Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Lymphoma, Large B-Cell, Diffuse
Brief summary
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).
Detailed description
The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.
Interventions
DRUGPolatuzumab Vedotin
Polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.
DRUGRituximab
Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.
DRUGGemcitabine
Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.
DRUGOxaliplatin
Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In stage 1 participants are all assigned to one group. In stage 2 participants are assigned to two groups in parallel for the duration of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL * Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that did not respond to or that progressed during therapy or progressed within 6 months (\< 6 months) of prior therapy) * At least one (≥ 1) line of prior systemic therapy: * Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; In such cases, salvage chemotherapy (e.g., rituximab, dexamethasone, cytarabine, and cisplatin \[R-DHAP\] and rituximab, ifosfamide, carboplatin, and etoposide phosphate \[R-ICE\]) will be counted as one line of therapy and conditioning chemotherapy (e.g., BEAM) followed by consolidative autologous HSCT will be counted as one line of therapy * Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; In such cases, salvage chemotherapy (e.g., R-DHAP and R-ICE) will be counted as one line of therapy and conditioning chemotherapy (e.g., carmustine, etoposide, cytarabine, and melphalan \[BEAM\]) followed by allogeneic HSCT will be counted as a separate line of therapy * Participants may have undergone CAR T-cell therapy prior to recruitment. In such cases, cell collection, conditioning chemotherapy, and infusion will be counted as one line of therapy. * Local therapies (e.g., radiotherapy) will not be considered as lines of treatment * For participants with a history of the transformation of indolent disease to DLBCL, it is preferred that participants have received at least one treatment for the transformed lymphoma. However, if there are cases where the participants have received an anthracycline-containing chemotherapy regimen (such as R-CHOP) for the indolent lymphoma only, then these participants can be considered as eligible. * At least one bi-dimensionally measurable lesion, defined as \> 1.5 cm in its longest dimension as measured by CT or MRI * Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 * Adequate hematological function * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm,
Exclusion criteria
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products * Contraindication to rituximab, gemcitabine or oxaliplatin * Peripheral neuropathy assessed to be \> Grade 1 according to NCI CTCAE v5.0 * Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks * Planned autologous or allogenic stem cell transplantation or CAR T-cell therapy at time of recruitment * Primary or secondary central nervous system (CNS) lymphoma * Richter's transformation or prior CLL * Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection * Vaccination with a live vaccine within 4 weeks prior to treatment * Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications * Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug * Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Number of Participants With Adverse Events (AEs) | From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage 1: Number of Participants With Peripheral Neuropathy (PN) | From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain. |
| Stage 2: Overall Survival (OS) | From randomization to death (Up to approximately 34 months) | OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator | Up to approximately 34 months | BOR was defined as the best response while on study (based on PET-CT or CT data) according to Lugano response criteria, as determined by the investigator. CMR and PMR based on PET-CT data were defined as outlined in the ORR outcome measure (OM) number 8. CT-based complete radiologic response was defined as target lymphatic nodes/nodal masses regression to ≤ 1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; absence of non-measured lesion; enlarged organs regress to normal; no new lesions and bone marrow normal by morphology, if indeterminate, immunohistochemistry (IHC) negative. CT-based partial response was defined as ≥50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of up to 6 target measurable nodes and extra nodal sites; absent/normal, regressed, but no increase in non-measured lesions; spleen regressed by \>50% in length beyond normal and no new lesions. Percentages are rounded off. |
| Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment | Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months | CRR was defined as the percentage of participants who had CMR based positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by investigator. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement is no greater than surrounding normal tissue even if the tissue has high physiologic uptake; no new lesions and no evidence of FDG-avid disease in bone marrow. Percentages are rounded off. |
| Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment | Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months | ORR=percentage of participants with CMR/PMR, based on PET-CT as determined by investigator per Lugano response criteria. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at LN & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off. |
| Stage 2: Duration of Response (DOR) | Up to approximately 34 months | DOR=time from the date of the first occurrence of a documented objective response (complete or partial response \[CR/PR\]) (based on PET-CT or CT data) as determined by the investigator, using Lugano response criteria, until PD (based on either response: including PET-CT data or not including any PET data) or death, whichever occurred first. CMR and PMR based on PET-CT data were defined as outlined in the ORR OM. CT-based complete and partial response were defined as outlined in the BOR OM. PD defined as outlined in the PFS OM. |
| Stage 1 and Stage 2: Event-free Survival (EFSeff) | Up to approximately 34 months | EFSeff was defined as the time from randomization to first to the earliest occurrence of the following: PD or relapse using Lugano response criteria (based on either response: including PET-CT data or not including any PET data); death due to any cause or initiation of any NALT. PD based on PET-CT data was defined as score 4 or 5 on 5PS with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New or recurrent FDG-avid foci. Participants with no EFSeff events were censored at the time of the last evaluable tumor assessment if post-baseline assessments were available and participants who did not undergo a post-baseline tumor assessment were censored at the time of randomization. KM method was used to estimate median EFS for each treatment arm. |
| Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30) | Up to approximately 34 months | Time to deterioration was defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health status and quality of life (GHS/QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). KM method was used to estimate median time to deterioration for each treatment arm. |
| Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30 | Up to approximately 34 months | Time to deterioration was defined as the time from randomization to the first documentation of a 10-point increase from baseline in EORTC QLQ-C30 fatigue scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) was scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). KM method was used to estimate median time to deterioration for each treatment arm. |
| Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS) | Up to approximately 34 months | Time to deterioration was defined as the time from randomization to the first documentation of a \>3-point decrease from baseline in FACT-Lym LymS. The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. KM method was used to estimate the median time to deterioration for each treatment arm. |
| Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months) | EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher physical functioning). |
| Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Baseline, Day 1 of Cycles 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months) | EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). A positive change from baseline indicates an improvement. |
| Stage 1 and Stage 2: Progression-free Survival (PFS) | From randomization to first occurrence of PD or death (Up to approximately 34 months) | PFS=time from randomization to the first occurrence of disease progression (PD) (based on either: PET-CT data/not including any PET data), as determined by investigator, per Lugano response criteria or death due to any cause, whichever occurs first. PD based on PET-CT data=score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver &/or new lesions) on 5-point scale (5PS) with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New/recurrent FDG-avid foci. Participants who did not report PD nor died at time of analysis were censored on the date of last evaluable tumor assessment if post-baseline tumor assessment or on date of randomization if no post-baseline tumor assessment. KM methodology was used to estimate median PFS. |
| Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7 and 8 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months) | The FACT/GOG-NTX scale provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It contains 12 items scored from 0-4, where 0=Not at all and 4=very much. Scores are summed for a range of 12-44, with lower scores indicating more severe neurotoxicity. Participants completed assessments until progression or non-protocol-specified anti-lymphoma treatment (NALT). Only records on or before the first NALT were summarized. |
| Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale | Up to approximately 34 months | EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). Clinically meaningful improvement was defined as a participant with at least a 7 point scale score increase. |
| Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale | Up to approximately 34 months | EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). Clinically meaningful improvement was defined as a participant with at least a 9 point scale score decrease. |
| Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS | Up to approximately 34 months | The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. Clinically meaningful improvement was defined as a 3-point increase from baseline. |
| Stage 2: Number of Participants With AEs | From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Stage 2: Number of Participants With PN | From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain. |
| Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin | Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months | Dose modifications (interruptions/reductions) were based on physical examination findings, observed toxicities, and laboratory results obtained within 72 hours before study treatment administration. The determination of all dose modifications was made based on the investigator's assessment of ongoing clinical benefit with continuing study treatment. Dosing occurred only when a participant's clinical assessment and laboratory test values were acceptable. |
| Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin | Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months | Dose intensity = (total dose actually received divided by the expected total dose)\*100. Expected total dose for dose intensity accounting for delay/reduction is based on the expected number of cycles between the first and last exposure of each drug. Percentage of dose intensity accounting for delay/reduction in dose by the participants in each arm is reported here. |
| Stage 1: OS | From randomization to the death (up to approximately 34 months) | OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. KM method was used to estimate median OS for each treatment arm. |
| Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin | Up to approximately 34 months | Treatment emergent ADA-positive participants after drug administration were determined for participants exposed to polatuzumab vedotin. Participants positive for treatment emergent ADA were defined as the number of post-baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = a participant with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Percentages are rounded off. |
| Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months) | The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. A positive change from baseline indicates an improvement. |
| Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment | Up to approximately 8.5 months | CRR was defined as the percentage of participants who had a complete metabolic response (CMR) based on positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by IRC. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Percentages are rounded off. |
| Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment | Up to approximately 8.5 months | ORR=percentage of participants with CMR/partial metabolic responses (PMR), based on PET-CT per Lugano response criteria as per an IRC. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at lymph nodes (LN) & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off. |
Countries
Brazil, Canada, China, Finland, France, Germany, Greece, India, Ireland, Italy, Mexico, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 270 participants with relapsed/refractory (r/r) diffuse large b-cell lymphoma (DLBCL) took part in the study at 64 investigative sites in 16 countries from 07 February 2020 to 29 November 2024.
Pre-assignment details
The study was divided into 2 stages: Stage 1, or safety run-in (SRI), and Stage 2, or randomized controlled trial (RCT). Participants received polatuzumab vedotin in combination with rituximab + gemcitabine + oxaliplatin (Pola-R-GemOx) during the SRI stage. Participants were randomized in a 1:1 ratio to receive either Pola-R-GemOx or rituximab + gemcitabine + oxaliplatin (R-GemOx) in the RCT stage.
Participants by arm
| Arm | Count |
|---|---|
| Stage 1: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles. | 15 |
| Stage 2: R-GemOx Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles. | 126 |
| Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles. | 129 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomized Controlled Trial | Death | 0 | 83 | 66 |
| Randomized Controlled Trial | Lost to Follow-up | 0 | 1 | 2 |
| Randomized Controlled Trial | Withdrawal by Subject | 0 | 10 | 6 |
| Safety Run-in | Death | 7 | 0 | 0 |
| Safety Run-in | Lost to Follow-up | 1 | 0 | 0 |
| Safety Run-in | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Stage 1: Pola-R-GemOx | Total | Stage 2: Pola-R-GemOx | Stage 2: R-GemOx |
|---|---|---|---|---|
| Age, Continuous | 70.7 years STANDARD_DEVIATION 12.6 | 63.1 years STANDARD_DEVIATION 14.2 | 63.0 years STANDARD_DEVIATION 14.5 | 62.2 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 54 Participants | 27 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 200 Participants | 97 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 16 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 16 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 91 Participants | 49 Participants | 41 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 9 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 14 Participants | 8 Participants | 6 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 10 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 130 Participants | 60 Participants | 56 Participants |
| Sex: Female, Male Female | 7 Participants | 128 Participants | 56 Participants | 65 Participants |
| Sex: Female, Male Male | 8 Participants | 142 Participants | 73 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 15 | 83 / 125 | 68 / 128 | 77 / 143 |
| other Total, other adverse events | 14 / 15 | 111 / 125 | 119 / 128 | 133 / 143 |
| serious Total, serious adverse events | 2 / 15 | 39 / 125 | 49 / 128 | 51 / 143 |
Outcome results
Primary
Stage 1: Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)
Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1: Number of Participants With Adverse Events (AEs) | 14 Participants |
Primary
Stage 1: Number of Participants With Peripheral Neuropathy (PN)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.
Time frame: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months)
Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1: Number of Participants With Peripheral Neuropathy (PN) | 8 Participants |
Primary
Stage 2: Overall Survival (OS)
OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm.
Time frame: From randomization to death (Up to approximately 34 months)
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Overall Survival (OS) | 12.5 months |
| Stage 2: Pola-R-GemOx | Stage 2: Overall Survival (OS) | 19.5 months |
p-value: 0.001795% CI: [0.43, 0.83]Log Rank
Secondary
Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment
CRR was defined as the percentage of participants who had CMR based positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by investigator. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement is no greater than surrounding normal tissue even if the tissue has high physiologic uptake; no new lesions and no evidence of FDG-avid disease in bone marrow. Percentages are rounded off.
Time frame: Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months
Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment | 20.0 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment | 18.3 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment | 35.7 percentage of participants |
95% CI: [5.95, 28.86]
Secondary
Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin
Dose intensity = (total dose actually received divided by the expected total dose)\*100. Expected total dose for dose intensity accounting for delay/reduction is based on the expected number of cycles between the first and last exposure of each drug. Percentage of dose intensity accounting for delay/reduction in dose by the participants in each arm is reported here.
Time frame: Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months
Population: Safety population included all participants who received any amount of any study drug (regardless of the stage).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin | 93.60 percentage of dose | Standard Deviation 11.23 |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin | 92.81 percentage of dose | Standard Deviation 10.33 |
Secondary
Stage 1 and Stage 2: Event-free Survival (EFSeff)
EFSeff was defined as the time from randomization to first to the earliest occurrence of the following: PD or relapse using Lugano response criteria (based on either response: including PET-CT data or not including any PET data); death due to any cause or initiation of any NALT. PD based on PET-CT data was defined as score 4 or 5 on 5PS with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New or recurrent FDG-avid foci. Participants with no EFSeff events were censored at the time of the last evaluable tumor assessment if post-baseline assessments were available and participants who did not undergo a post-baseline tumor assessment were censored at the time of randomization. KM method was used to estimate median EFS for each treatment arm.
Time frame: Up to approximately 34 months
Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Event-free Survival (EFSeff) | 3.9 months |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Event-free Survival (EFSeff) | 2.7 months |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Event-free Survival (EFSeff) | 6.8 months |
95% CI: [0.3, 0.53]
Secondary
Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin
Dose modifications (interruptions/reductions) were based on physical examination findings, observed toxicities, and laboratory results obtained within 72 hours before study treatment administration. The determination of all dose modifications was made based on the investigator's assessment of ongoing clinical benefit with continuing study treatment. Dosing occurred only when a participant's clinical assessment and laboratory test values were acceptable.
Time frame: Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months
Population: Safety population included all participants who received any amount of any study drug (regardless of the stage).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin | 3 Participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin | 22 Participants |
Secondary
Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment
ORR=percentage of participants with CMR/PMR, based on PET-CT as determined by investigator per Lugano response criteria. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at LN & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.
Time frame: Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months
Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment | 26.7 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment | 24.6 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment | 45.0 percentage of participants |
95% CI: [8.16, 32.56]
Secondary
Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin
Treatment emergent ADA-positive participants after drug administration were determined for participants exposed to polatuzumab vedotin. Participants positive for treatment emergent ADA were defined as the number of post-baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = a participant with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Percentages are rounded off.
Time frame: Up to approximately 34 months
Population: Immunogenicity-evaluable population included all participants who received at least one dose of polatuzumab vedotin with at least one evaluable post-baseline ADA sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin | 0 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin | 2.6 percentage of participants |
Secondary
Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator
BOR was defined as the best response while on study (based on PET-CT or CT data) according to Lugano response criteria, as determined by the investigator. CMR and PMR based on PET-CT data were defined as outlined in the ORR outcome measure (OM) number 8. CT-based complete radiologic response was defined as target lymphatic nodes/nodal masses regression to ≤ 1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; absence of non-measured lesion; enlarged organs regress to normal; no new lesions and bone marrow normal by morphology, if indeterminate, immunohistochemistry (IHC) negative. CT-based partial response was defined as ≥50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of up to 6 target measurable nodes and extra nodal sites; absent/normal, regressed, but no increase in non-measured lesions; spleen regressed by \>50% in length beyond normal and no new lesions. Percentages are rounded off.
Time frame: Up to approximately 34 months
Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator | 46.7 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator | 34.9 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator | 65.1 percentage of participants |
95% CI: [17.71, 42.68]
Secondary
Stage 1 and Stage 2: Progression-free Survival (PFS)
PFS=time from randomization to the first occurrence of disease progression (PD) (based on either: PET-CT data/not including any PET data), as determined by investigator, per Lugano response criteria or death due to any cause, whichever occurs first. PD based on PET-CT data=score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver &/or new lesions) on 5-point scale (5PS) with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New/recurrent FDG-avid foci. Participants who did not report PD nor died at time of analysis were censored on the date of last evaluable tumor assessment if post-baseline tumor assessment or on date of randomization if no post-baseline tumor assessment. KM methodology was used to estimate median PFS.
Time frame: From randomization to first occurrence of PD or death (Up to approximately 34 months)
Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1 and Stage 2: Progression-free Survival (PFS) | 3.9 months |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Progression-free Survival (PFS) | 2.7 months |
| Stage 2: Pola-R-GemOx | Stage 1 and Stage 2: Progression-free Survival (PFS) | 7.4 months |
p-value: <0.000195% CI: [0.27, 0.51]Log Rank
Secondary
Stage 1: OS
OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. KM method was used to estimate median OS for each treatment arm.
Time frame: From randomization to the death (up to approximately 34 months)
Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 1: OS | 12.6 months |
Secondary
Stage 2: Change From Baseline in FACT-Lym LYMS Scores
The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. A positive change from baseline indicates an improvement.
Time frame: Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants may have been lost to follow-up/did not complete the specified visit during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 13 | 13.00 score on a scale | — |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 2 Day 1 | 0.49 score on a scale | Standard Deviation 9.37 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 05 | 6.00 score on a scale | Standard Deviation 9.56 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 06 | 5.89 score on a scale | Standard Deviation 6.75 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 3 Day 1 | 1.71 score on a scale | Standard Deviation 8.17 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 5 Day 1 | 1.95 score on a scale | Standard Deviation 8.15 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 7 Day 1 | 0.32 score on a scale | Standard Deviation 8.23 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at End of Treatment | -0.71 score on a scale | Standard Deviation 10.34 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 01 | 0.14 score on a scale | Standard Deviation 13.1 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 02 | 5.22 score on a scale | Standard Deviation 9.28 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 03 | 4.08 score on a scale | Standard Deviation 7.31 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 04 | 6.00 score on a scale | Standard Deviation 6.18 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 07 | 5.29 score on a scale | Standard Deviation 7.54 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 08 | 8.00 score on a scale | Standard Deviation 4.53 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 09 | 8.80 score on a scale | Standard Deviation 5.81 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 10 | 7.50 score on a scale | Standard Deviation 7.23 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 11 | 5.67 score on a scale | Standard Deviation 7.02 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 12 | 5.50 score on a scale | Standard Deviation 0.71 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Baseline | 41.73 score on a scale | Standard Deviation 10.88 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 10 | 4.00 score on a scale | Standard Deviation 3.32 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 01 | 2.88 score on a scale | Standard Deviation 10.03 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Baseline | 42.49 score on a scale | Standard Deviation 10.94 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 08 | 5.82 score on a scale | Standard Deviation 5.46 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 04 | 4.29 score on a scale | Standard Deviation 6.47 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 02 | 5.32 score on a scale | Standard Deviation 8.15 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 05 | 4.07 score on a scale | Standard Deviation 6.87 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 12 | 4.50 score on a scale | Standard Deviation 4.95 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 07 | 4.65 score on a scale | Standard Deviation 7.56 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 13 | 4.00 score on a scale | Standard Deviation 4.24 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 14 | 8.00 score on a scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 2 Day 1 | 2.12 score on a scale | Standard Deviation 8.38 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 03 | 3.90 score on a scale | Standard Deviation 7.32 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 3 Day 1 | 2.66 score on a scale | Standard Deviation 9.22 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 09 | 7.82 score on a scale | Standard Deviation 6.63 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 5 Day 1 | 3.53 score on a scale | Standard Deviation 8.1 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 06 | 4.15 score on a scale | Standard Deviation 6.16 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Cycle 7 Day 1 | 2.69 score on a scale | Standard Deviation 10.45 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at Long-term Follow-up 11 | 6.75 score on a scale | Standard Deviation 5.44 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in FACT-Lym LYMS Scores | Change at End of Treatment | 2.34 score on a scale | Standard Deviation 11.09 |
Secondary
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30
EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). A positive change from baseline indicates an improvement.
Time frame: Baseline, Day 1 of Cycles 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants may have been lost to follow-up/did not complete the specified visit during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 02 | -8.77 score on a scale | Standard Deviation 15.96 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 13 | 22.22 score on a scale | — |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 03 | 1.59 score on a scale | Standard Deviation 24.6 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Baseline | 34.99 score on a scale | Standard Deviation 25 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 04 | -1.71 score on a scale | Standard Deviation 17.48 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 06 | 0.00 score on a scale | Standard Deviation 25.66 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 2 Day 1 | 2.81 score on a scale | Standard Deviation 25.16 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 07 | 8.33 score on a scale | Standard Deviation 17.57 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at End of Treatment | 7.43 score on a scale | Standard Deviation 26.7 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 09 | 0.00 score on a scale | Standard Deviation 23.31 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 5 Day 1 | 4.26 score on a scale | Standard Deviation 25.44 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 10 | 8.89 score on a scale | Standard Deviation 19.88 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 05 | 0.00 score on a scale | Standard Deviation 24.34 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 11 | 11.11 score on a scale | Standard Deviation 12.83 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 7 Day 1 | 4.90 score on a scale | Standard Deviation 17.56 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 12 | 0.00 score on a scale | Standard Deviation 19.24 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 3 Day 1 | 2.04 score on a scale | Standard Deviation 23.08 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 01 | 3.03 score on a scale | Standard Deviation 18.84 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 08 | 0.00 score on a scale | Standard Deviation 17.21 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 2 Day 1 | 2.57 score on a scale | Standard Deviation 20.3 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 14 | -22.22 score on a scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at End of Treatment | 6.99 score on a scale | Standard Deviation 28.87 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 04 | -9.68 score on a scale | Standard Deviation 18.97 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 07 | -8.50 score on a scale | Standard Deviation 16.91 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Baseline | 35.13 score on a scale | Standard Deviation 28.01 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 3 Day 1 | 0.05 score on a scale | Standard Deviation 24.39 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 5 Day 1 | -0.45 score on a scale | Standard Deviation 24.88 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Cycle 7 Day 1 | 0.48 score on a scale | Standard Deviation 27.38 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 01 | -0.67 score on a scale | Standard Deviation 23.37 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 02 | -4.97 score on a scale | Standard Deviation 19.96 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 03 | -6.27 score on a scale | Standard Deviation 18.52 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 05 | -7.66 score on a scale | Standard Deviation 21.23 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 06 | -7.26 score on a scale | Standard Deviation 12.94 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 08 | -10.10 score on a scale | Standard Deviation 12.62 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 09 | -12.12 score on a scale | Standard Deviation 16.82 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 10 | -2.22 score on a scale | Standard Deviation 4.97 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 11 | -8.33 score on a scale | Standard Deviation 16.67 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 12 | -11.11 score on a scale | Standard Deviation 15.71 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 13 | -11.11 score on a scale | Standard Deviation 15.71 |
Secondary
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores
The FACT/GOG-NTX scale provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It contains 12 items scored from 0-4, where 0=Not at all and 4=very much. Scores are summed for a range of 12-44, with lower scores indicating more severe neurotoxicity. Participants completed assessments until progression or non-protocol-specified anti-lymphoma treatment (NALT). Only records on or before the first NALT were summarized.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7 and 8 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints. Participants may have been lost to follow-up/did not complete the specified visit during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 12 | -0.33 score on scale | Standard Deviation 4.16 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Baseline | 40.67 score on scale | Standard Deviation 6.7 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 2 Day 1 | -1.56 score on scale | Standard Deviation 5.6 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 3 Day 1 | -1.35 score on scale | Standard Deviation 4.91 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 4 Day 1 | -2.44 score on scale | Standard Deviation 6.82 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 5 Day 1 | -2.35 score on scale | Standard Deviation 4.54 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 6 Day 1 | -2.02 score on scale | Standard Deviation 5.47 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 7 Day 1 | -2.00 score on scale | Standard Deviation 4.77 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 8 Day 1 | -3.62 score on scale | Standard Deviation 4.95 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at End of Treatment | -3.80 score on scale | Standard Deviation 7.65 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 01 | -4.91 score on scale | Standard Deviation 9.11 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 02 | -3.77 score on scale | Standard Deviation 7 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 03 | -4.73 score on scale | Standard Deviation 7.22 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 04 | -0.85 score on scale | Standard Deviation 6.35 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 05 | -1.55 score on scale | Standard Deviation 3.91 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 06 | -1.20 score on scale | Standard Deviation 5.22 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 07 | -3.00 score on scale | Standard Deviation 6.55 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 08 | 0.83 score on scale | Standard Deviation 5.71 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 09 | 0.83 score on scale | Standard Deviation 5.56 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 10 | 1.20 score on scale | Standard Deviation 7.4 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 11 | -1.50 score on scale | Standard Deviation 4.8 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 13 | -5.00 score on scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 02 | -6.86 score on scale | Standard Deviation 7.75 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 12 | -1.50 score on scale | Standard Deviation 0.71 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 03 | -7.73 score on scale | Standard Deviation 7.04 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Baseline | 40.37 score on scale | Standard Deviation 8.32 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 09 | -4.20 score on scale | Standard Deviation 4.42 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 2 Day 1 | -0.54 score on scale | Standard Deviation 6.87 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 04 | -5.18 score on scale | Standard Deviation 5.96 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 3 Day 1 | -0.20 score on scale | Standard Deviation 8.01 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 14 | 39.00 score on scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 4 Day 1 | -0.78 score on scale | Standard Deviation 7.58 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 05 | -4.92 score on scale | Standard Deviation 5.85 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 5 Day 1 | -1.68 score on scale | Standard Deviation 7.95 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 10 | -4.60 score on scale | Standard Deviation 6.02 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 6 Day 1 | -3.48 score on scale | Standard Deviation 8.92 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 06 | -4.58 score on scale | Standard Deviation 6.79 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 7 Day 1 | -4.25 score on scale | Standard Deviation 9.97 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 13 | -2.00 score on scale | Standard Deviation 0 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Cycle 8 Day 1 | -5.08 score on scale | Standard Deviation 10.41 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 07 | -3.62 score on scale | Standard Deviation 6.18 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at End of Treatment | -5.96 score on scale | Standard Deviation 11.05 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 11 | -1.50 score on scale | Standard Deviation 1.91 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 01 | -9.50 score on scale | Standard Deviation 11 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores | Change at Long-term Follow-up 08 | -3.05 score on scale | Standard Deviation 7.02 |
Secondary
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30
EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher physical functioning).
Time frame: Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified timepoint. Participants may have been lost to follow-up/did not complete the specified visit during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 01 | 0.91 score on a scale | Standard Deviation 19.66 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 05 | 7.88 score on a scale | Standard Deviation 19.28 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 08 | 14.44 score on a scale | Standard Deviation 21.26 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 10 | 18.67 score on a scale | Standard Deviation 18.5 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 12 | 13.33 score on a scale | Standard Deviation 11.55 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Baseline | 65.65 score on a scale | Standard Deviation 22.83 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 2 Day 1 | -0.88 score on a scale | Standard Deviation 16.6 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 3 Day 1 | -1.10 score on a scale | Standard Deviation 19.81 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 5 Day 1 | 1.28 score on a scale | Standard Deviation 17 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 7 Day 1 | -1.76 score on a scale | Standard Deviation 18.37 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at End of Treatment | -4.65 score on a scale | Standard Deviation 19 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 02 | 10.53 score on a scale | Standard Deviation 17.54 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 03 | 4.29 score on a scale | Standard Deviation 19.5 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 04 | 6.67 score on a scale | Standard Deviation 15.87 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 06 | 10.00 score on a scale | Standard Deviation 15.48 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 07 | 9.17 score on a scale | Standard Deviation 17.43 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 09 | 16.67 score on a scale | Standard Deviation 17.26 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 11 | 5.00 score on a scale | Standard Deviation 11.39 |
| Stage 1: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 13 | 6.67 score on a scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 13 | 16.67 score on a scale | Standard Deviation 23.57 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at End of Treatment | -3.70 score on a scale | Standard Deviation 22.56 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 03 | 0.17 score on a scale | Standard Deviation 18.51 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 01 | -0.80 score on a scale | Standard Deviation 20.1 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 07 | 6.67 score on a scale | Standard Deviation 17.95 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 08 | 5.45 score on a scale | Standard Deviation 16.01 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 02 | 2.28 score on a scale | Standard Deviation 20.11 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 11 | 11.67 score on a scale | Standard Deviation 15.75 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 14 | 33.33 score on a scale | — |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 12 | 16.67 score on a scale | Standard Deviation 23.57 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 09 | 8.48 score on a scale | Standard Deviation 19.57 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Baseline | 71.08 score on a scale | Standard Deviation 25.09 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 04 | 0.65 score on a scale | Standard Deviation 14.54 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 2 Day 1 | 0.94 score on a scale | Standard Deviation 16.74 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 05 | -2.53 score on a scale | Standard Deviation 18.89 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 3 Day 1 | 2.16 score on a scale | Standard Deviation 19.57 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 10 | 5.33 score on a scale | Standard Deviation 19.66 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 5 Day 1 | 2.68 score on a scale | Standard Deviation 20.65 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Long-term Follow-up 06 | 1.54 score on a scale | Standard Deviation 16.79 |
| Stage 2: Pola-R-GemOx | Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 | Change at Cycle 7 Day 1 | 0.87 score on a scale | Standard Deviation 20.39 |
Secondary
Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment
CRR was defined as the percentage of participants who had a complete metabolic response (CMR) based on positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by IRC. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Percentages are rounded off.
Time frame: Up to approximately 8.5 months
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment | 19.0 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment | 40.3 percentage of participants |
p-value: <0.000195% CI: [9.58, 32.94]Cochran-Mantel-Haenszel
Secondary
Stage 2: Duration of Response (DOR)
DOR=time from the date of the first occurrence of a documented objective response (complete or partial response \[CR/PR\]) (based on PET-CT or CT data) as determined by the investigator, using Lugano response criteria, until PD (based on either response: including PET-CT data or not including any PET data) or death, whichever occurred first. CMR and PMR based on PET-CT data were defined as outlined in the ORR OM. CT-based complete and partial response were defined as outlined in the BOR OM. PD defined as outlined in the PFS OM.
Time frame: Up to approximately 34 months
Population: DOR-evaluable population included all participants who had an objective response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Duration of Response (DOR) | 8.5 months |
| Stage 2: Pola-R-GemOx | Stage 2: Duration of Response (DOR) | 11.8 months |
Secondary
Stage 2: Number of Participants With AEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)
Population: Safety-evaluable population included all participants who received any amount of any study drug (regardless of the stage).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Number of Participants With AEs | 117 Participants |
| Stage 2: Pola-R-GemOx | Stage 2: Number of Participants With AEs | 125 Participants |
Secondary
Stage 2: Number of Participants With PN
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.
Time frame: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)
Population: Safety-evaluable population included all participants who received any amount of any study drug (regardless of the stage).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Number of Participants With PN | 36 Participants |
| Stage 2: Pola-R-GemOx | Stage 2: Number of Participants With PN | 73 Participants |
Secondary
Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment
ORR=percentage of participants with CMR/partial metabolic responses (PMR), based on PET-CT per Lugano response criteria as per an IRC. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at lymph nodes (LN) & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.
Time frame: Up to approximately 8.5 months
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment | 24.6 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment | 52.7 percentage of participants |
p-value: <0.000195% CI: [15.89, 40.33]Cochran-Mantel-Haenszel
Secondary
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale
EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). Clinically meaningful improvement was defined as a participant with at least a 9 point scale score decrease.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants in Stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale | 46.0 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale | 55.8 percentage of participants |
95% CI: [-3.22, 22.78]
Secondary
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale
EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). Clinically meaningful improvement was defined as a participant with at least a 7 point scale score increase.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants in Stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale | 31.0 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale | 41.1 percentage of participants |
95% CI: [-2.37, 22.63]
Secondary
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS
The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. Clinically meaningful improvement was defined as a 3-point increase from baseline.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants in Stage 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS | 48.4 percentage of participants |
| Stage 2: Pola-R-GemOx | Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS | 66.7 percentage of participants |
95% CI: [5.54, 30.97]
Secondary
Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30
Time to deterioration was defined as the time from randomization to the first documentation of a 10-point increase from baseline in EORTC QLQ-C30 fatigue scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) was scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). KM method was used to estimate median time to deterioration for each treatment arm.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30 | 1.4 months |
| Stage 2: Pola-R-GemOx | Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30 | 1.8 months |
95% CI: [0.62, 1.17]
Secondary
Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS)
Time to deterioration was defined as the time from randomization to the first documentation of a \>3-point decrease from baseline in FACT-Lym LymS. The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0=Not at all and 4=very much. Scale score range is from 0 to 60. Higher score indicates better quality of life. KM method was used to estimate the median time to deterioration for each treatment arm.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS) | 2.5 months |
| Stage 2: Pola-R-GemOx | Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS) | 4.6 months |
95% CI: [0.45, 0.91]
Secondary
Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)
Time to deterioration was defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health status and quality of life (GHS/QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from not at all to very much. Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). KM method was used to estimate median time to deterioration for each treatment arm.
Time frame: Up to approximately 34 months
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage 1: Pola-R-GemOx | Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30) | 2.8 months |
| Stage 2: Pola-R-GemOx | Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30) | 8.1 months |
95% CI: [0.4, 0.83]