Follicular Lymphoma, Lymphoma, Large B-Cell, Diffuse
Conditions
Brief summary
This Phase Ib/II, open-label, multicenter, non-randomized, dose-escalation study will evaluate the safety, efficacy, and pharmacokinetics of obinutuzumab in combination with idasanutlin and venetoclax in participants with R/R FL and obinutuzumab or rituximab in combination with idasanutlin and venetoclax in participants with R/R DLBCL. The study will include an initial dose-escalation phase followed by an expansion phase. The dose-escalation phase is designed to determine the recommended phase II doses (RP2Ds) and regimen for idasanutlin and venetoclax in combination with obinutuzumab for FL participants and in combination with rituximab for DLBCL participants.
Interventions
DRUGIdasanutlin
Induction Treatment: Idasanutlin tablets will be administered orally once daily at escalated doses (starting dose 100 milligrams \[mg\], maximum 600 mg). Post-Induction Treatment: The dose and regimen will be determined by the Sponsor after review of all relevant data. The dose for maintenance/consolidation will not exceed the dose the participant received during induction.
DRUGObinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 mg by intravenous (IV) infusion on Days 1, 8 and 15 of Cycle 1 and on Day 1 of each subsequent cycle (Cycles 2 to 6) (each cycle = 28 days) during induction treatment, and on Day 1 of every other month during maintenance treatment (eligible participants with FL only) or during consolidation treatment (eligible participants with DLBCL only).
DRUGVenetoclax
Induction Treatment: Venetoclax tablets will be administered orally once daily at escalated doses (starting dose 200 mg, maximum 800 mg). Post-Induction Treatment: The dose and regimen will be determined by the Sponsor after review of all relevant data. The dose for maintenance/consolidation will not exceed the dose the participant received during induction.
DRUGRituximab
Rituximab will be administered by IV infusion at a dose of 375 milligrams per square meter (mg/m\^2) on Day 1 of Cycles 1-6 during induction treatment and on Day 1 of every other month during consolidation treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * B-cell lymphoma classified as either of the following: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) monoclonal antibody; R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in participants who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation, have failed second line combination chemotherapy, or experienced disease progression following autologous stem-cell transplantation * Histologically documented CD20-positive lymphoma * Fluorodeoxyglucose (FDG)-avid lymphoma (that is \[i.e.\], PET-positive lymphoma) * At least one bi-dimensionally measurable lesion (greater than \[\>\] 1.5 centimeters \[cm\] in its largest dimension by CT scan or magnetic resonance imaging \[MRI\]) * Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Exclusion criteria
* Known CD20-negative status at relapse or progression * Prior allogeneic stem-cell transplantation (SCT) * Completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 * Prior standard or investigational anti-cancer therapy as specified: Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1; Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1 * Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade less than or equal to (\</=) 2 (according to National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0) prior to Day 1 of Cycle 1 * Grade 3b FL * History of transformation of indolent disease to DLBCL (expansion-phase only) * Central nervous system lymphoma or leptomeningeal infiltration * Treatment with systemic corticosteroids \>20 mg/day, prednisone or equivalent * Clinical conditions requiring treatment with oral or parenteral anticoagulants or antiplatelet agents unless treatment can be discontinued 7 days (or 5 half-lives) prior to initiation of study treatment (except used as flushes for indwelling catheters) * History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies * Known hypersensitivity or allergy to murine products or any component of the obinutuzumab, rituximab, idasanutlin, or venetoclax formulation * Current or history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or HCV antibody at screening * History of progressive multifocal leukoencephalopathy (PML) * History of other malignancy that could affect compliance with the protocol or interpretation of results * Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results * Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by study treatment, such as severe hereditary coagulation disorders or insulin-dependent diabetes mellitus that is not optimally controlled with medical management (example, presence of ketoacidosis) * Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the study * Inadequate hematologic function (unless due to underlying lymphoma), defined as follows: Hemoglobin less than (\<) 9 grams per decilitre (g/dL), absolute neutrophil count (ANC) \<1.5\*10\^9 cells per liter (cells/L), platelet count \<75\*10\^9 cells/L * Any of the following abnormal laboratory values (unless due to underlying lymphoma): International normalized ratio (INR) or prothrombin time (PT) \>1.5\*upper limit of normal (ULN) in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) \>1.5\*ULN in the absence of a lupus anticoagulant * Life expectancy \<3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days) | It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. phases. The study was closed because at escalation doses 100 (in combination with venetoclax 400 mg) and 150 mg (in combination with venetoclax 200 mg) Idasanutlin, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The subpopulations of DLBCL and FL were showed no difference in their genetic subtype make-up, therefore, Cohorts Safety, 1, 2, 3 contain both populations. The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3. |
| RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days) | It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. The study was closed because at escalation doses 200 (in combination with 150 mg idasanutlin) and 400 (in combination with 100 mg idasanutlin) mg Venetoclax, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3. |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days) | DLT is defined as any one of the following events occurring during first two Cycles of treatment and assessed by the investigator as clearly not related to patient's underlying disease: - Any Grade 5 adverse event (AE) unless unequivocally due to the underlying malignancy or extraneous causes; - AE of any grade that leads to a delay of more than 14 days at the start of next treatment cycle; - Hematologic AEs (neutropenia, thrombocytopenia); - Non-hematologic AE, except IRRs, laboratory TLS without manifestations of clinical TLS, AST or ALT, diarrhea, nausea or vomiting, fatigue, asthenia, anorexia, or constipation, hepatic transaminase. |
| Percentage of Participants With Adverse Events (AEs) | From Baseline up to approximately 48 months | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a casual relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Percentage of Participants With Complete Response (CR), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography-Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria | At end of Induction (EOI) (within 6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]) | The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I). Therefore the result data not derived and not reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/nomal, regressed, but no increase; and spleen must have regressed by \>50% in length. Therefore the result data not derived and not reported. The study was pre-maturely terminated. |
| Percentage of Participants With Objective Response at EOI, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. The study was pre-maturely terminated at escalation phase. |
| Percentage of Participants With Objective Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria | From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months | The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. The study was pre-maturely terminated at escalation phase. |
| Observed Serum Concentration of Obinutuzumab in Participants With FL | From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description) | Observed Serum Concentration of Obinutuzumab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study. |
| Observed Serum Concentration of Obinutuzumab in Participants With DLBCL | Induction: Pre-dose (any time prior to dose on same day) and 30 min post-dose on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) and 30 min post-dose on Day 1 of Cycles 2, 4 and 6 (each cycle = 28 days) | Observed Serum Concentration of Obinutuzumab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported. |
| Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based complete response (CR), which required a complete metabolic response with a score of 1, 2 or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[\<=\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and \<= liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if intermediate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders. |
| Observed Serum Concentration of Rituximab in Participants With DLBCL | From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description) | Observed Serum Concentration of Rituximab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported. |
| Observed Plasma Concentration of Idasanutlin in Participants With FL | From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description) | Observed Plasma Concentration of Idasanutlin in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported |
| Observed Plasma Concentration of Idasanutlin in Participants With DLBCL | From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description) | Observed Plasma Concentration of Idasanutlin in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported |
| Observed Plasma Concentration of Venetoclax in Participants With FL | From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description) | Observed Plasma Concentration of Venetoclax in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. |
| Observed Plasma Concentration of Venetoclax in Participants With DLBCL | From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description) | Observed Plasma Concentration of Venetoclax in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. |
| Observed Serum Concentration of Rituximab in Participants With FL | Induction: Pre-dose (any time prior to dose on same day) on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) on Day 1 of Cycles 2, 4, 6; 30 min post-dose on Day 1 of Cycles 1 and 6 (each cycle = 28 days) | Observed Serum Concentration of Rituximab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported. |
| Percentage of Participants With CR, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required to complete radiologic response with all of the following: target nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. Therefore the result data not derived and not reported. |
| Percentage of Participants With CR, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who received at least 2 cycles of Induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. This outcome measure therefore not derived and not reported. |
| Percentage of Participants With Objective Response, Determined by the IRC on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The IRC was to evaluate responses at the end of induction treatment using Luagno 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2 or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Therefore the result data not derived and not reported. The study was pre-maturely terminated. |
| Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days] | The investigator was to evaluate responses at end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders. |
Countries
Australia, Germany, New Zealand, South Korea, United States
Participant flow
Recruitment details
29 Participants (ITT population) were enrolled at 13 sites in the USA, Australia, South Korea, New Zealand and Germany during the dose escalation phase. 1 participant was undefined as the diagnosis at study entry was not provided. Due to the study's pre-mature termination, the planned Dose Expansion Phase did not take place for both arms DLBCL and FL.
Pre-assignment details
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase. In each DLBCL and FL arm, participants are in Safety Cohort, Cohort 1, Cohort 2, Cohort 3 and Cohort 3- Not defined (DLBCL only). All Adverse Events are reported per Cohort rather than per Arm.
Participants by arm
| Arm | Count |
|---|---|
| Dose-Escalation DLBCL and FL Safety Cohort Idasanutlin 100 mg + venetoclax 200 mg + obinutuzumab 1000 mg | 9 |
| Dose-Escalation DLBCL and FL Cohort 1 Idasanutlin 100 mg + venetoclax 200 mg + obinutuzumab 1000 mg | 6 |
| Dose Escaltion DLBCL and FL Cohort 2 Idasanutlin 150 mg + venetoclax 200 mg + obinutuzumab 1000 mg | 7 |
| Dose Escalation DLBCL and FL Cohort 3 Idasanutlin 100 mg + venetoclax 400 mg + obinutuzumab 1000 mg | 6 |
| Not Defined for DLBCL or FL Subgroups Cohort 3 Idasanutlin 100 mg+ Venetoclax 200mg + obinutuzumab 1000 mg | 1 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 2 | 2 | 2 | 0 |
| Overall Study | discontinued due to worsening of pre-existing medical condition | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Progression of disease | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 2 | 4 | 4 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Dose-Escalation DLBCL and FL Safety Cohort | Dose-Escalation DLBCL and FL Cohort 1 | Dose Escaltion DLBCL and FL Cohort 2 | Dose Escalation DLBCL and FL Cohort 3 | Not Defined for DLBCL or FL Subgroups Cohort 3 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 15.5 | 68.5 Years STANDARD_DEVIATION 8.7 | 72.4 Years STANDARD_DEVIATION 8.6 | 74.3 Years STANDARD_DEVIATION 5.5 | 25.0 Years STANDARD_DEVIATION 0 | 66.1 Years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 6 Participants | 7 Participants | 6 Participants | 1 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 6 Participants | 2 Participants | 1 Participants | 21 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 9 | 2 / 6 | 2 / 7 | 2 / 6 | 0 / 1 |
| other Total, other adverse events | 9 / 9 | 6 / 6 | 7 / 7 | 6 / 6 | 0 / 1 |
| serious Total, serious adverse events | 3 / 9 | 3 / 6 | 4 / 7 | 4 / 6 | 0 / 1 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a casual relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: From Baseline up to approximately 48 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | Percentage of Participants With Adverse Events (AEs) | 100 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 1 | Percentage of Participants With Adverse Events (AEs) | 100 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 2 | Percentage of Participants With Adverse Events (AEs) | 100 Percentage of Participants |
| Dose Escalation DLBCL and FL Cohort 3 | Percentage of Participants With Adverse Events (AEs) | 100 Percentage of Participants |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | Percentage of Participants With Adverse Events (AEs) | 0 Percentage of Participants |
Primary
Percentage of Participants With Complete Response (CR), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography-Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I). Therefore the result data not derived and not reported.
Time frame: At end of Induction (EOI) (within 6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days])
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).
Primary
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
DLT is defined as any one of the following events occurring during first two Cycles of treatment and assessed by the investigator as clearly not related to patient's underlying disease: - Any Grade 5 adverse event (AE) unless unequivocally due to the underlying malignancy or extraneous causes; - AE of any grade that leads to a delay of more than 14 days at the start of next treatment cycle; - Hematologic AEs (neutropenia, thrombocytopenia); - Non-hematologic AE, except IRRs, laboratory TLS without manifestations of clinical TLS, AST or ALT, diarrhea, nausea or vomiting, fatigue, asthenia, anorexia, or constipation, hepatic transaminase.
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Population: Safety-Evaluable Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 1 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 16.7 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 2 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 28.6 Percentage of Participants |
| Dose Escalation DLBCL and FL Cohort 3 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 16.7 Percentage of Participants |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0 Percentage of Participants |
Primary
RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. phases. The study was closed because at escalation doses 100 (in combination with venetoclax 400 mg) and 150 mg (in combination with venetoclax 200 mg) Idasanutlin, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The subpopulations of DLBCL and FL were showed no difference in their genetic subtype make-up, therefore, Cohorts Safety, 1, 2, 3 contain both populations. The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Dose Escaltion DLBCL and FL Cohort 1 | RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Dose Escaltion DLBCL and FL Cohort 2 | RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | 150 mg |
| Dose Escalation DLBCL and FL Cohort 3 | RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab | NA mg |
Primary
RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. The study was closed because at escalation doses 200 (in combination with 150 mg idasanutlin) and 400 (in combination with 100 mg idasanutlin) mg Venetoclax, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Dose Escaltion DLBCL and FL Cohort 1 | RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Dose Escaltion DLBCL and FL Cohort 2 | RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | 200 mg |
| Dose Escalation DLBCL and FL Cohort 3 | RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | NA mg |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab | NA mg |
Secondary
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Time frame: From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Plasma Concentration of Idasanutlin in Participants With FL
Observed Plasma Concentration of Idasanutlin in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Time frame: From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Plasma Concentration of Venetoclax in Participants With DLBCL
Observed Plasma Concentration of Venetoclax in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Time frame: From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Plasma Concentration of Venetoclax in Participants With FL
Observed Plasma Concentration of Venetoclax in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Time frame: From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time frame: Induction: Pre-dose (any time prior to dose on same day) and 30 min post-dose on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) and 30 min post-dose on Day 1 of Cycles 2, 4 and 6 (each cycle = 28 days)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Serum Concentration of Obinutuzumab in Participants With FL
Observed Serum Concentration of Obinutuzumab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Time frame: From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Serum Concentration of Rituximab in Participants With DLBCL
Observed Serum Concentration of Rituximab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time frame: From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Observed Serum Concentration of Rituximab in Participants With FL
Observed Serum Concentration of Rituximab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place. The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time frame: Induction: Pre-dose (any time prior to dose on same day) on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) on Day 1 of Cycles 2, 4, 6; 30 min post-dose on Day 1 of Cycles 1 and 6 (each cycle = 28 days)
Population: ITT Population was planned. Due to the pre-mature study termination, no participants were available for this endpoint and result data were not collected.
Secondary
Percentage of Participants With CR, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who received at least 2 cycles of Induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. This outcome measure therefore not derived and not reported.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: ITT Population; exploratory analysis of the dose escalation phase (Part I). The study plan was for efficacy analyses to be based on responses in participants enrolled during expansion phase (Part II), but it was not opened (i.e., no enrollment) and at the study was terminated early.
Secondary
Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based complete response (CR), which required a complete metabolic response with a score of 1, 2 or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to \[\<=\] mediastinum; 3 = uptake greater than \[\>\] mediastinum and \<= liver; 4 = uptake moderately \> liver; 5 = uptake markedly \> liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if intermediate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: ITT Population; exploratory analysis of the dose escalation phase (Part I). The study plan was for efficacy analyses to be based on responses in participants enrolled during the expansion phase (Part II), but it was not opened (i.e., no enrollment) and at the study was terminated early.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 22.2 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 1 | Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 16.7 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 2 | Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 28.6 Percentage of Participants |
| Dose Escalation DLBCL and FL Cohort 3 | Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 16.7 Percentage of Participants |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 0 Percentage of Participants |
Secondary
Percentage of Participants With CR, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required to complete radiologic response with all of the following: target nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion \[LDi\]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. Therefore the result data not derived and not reported.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e. , no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).
Secondary
Percentage of Participants With Objective Response at EOI, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. The study was pre-maturely terminated at escalation phase.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II)., but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).
Secondary
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation DLBCL and FL Safety Cohort | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 33.3 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 1 | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 16.7 Percentage of Participants |
| Dose Escaltion DLBCL and FL Cohort 2 | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 28.6 Percentage of Participants |
| Dose Escalation DLBCL and FL Cohort 3 | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 33.3 Percentage of Participants |
| Not Defined for DLBCL or FL Subgroups Cohort 3 | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria | 0 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/nomal, regressed, but no increase; and spleen must have regressed by \>50% in length. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II)., but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).
Secondary
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using Luagno 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2 or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 \[no uptake above background\] to 5 \[uptake markedly higher than liver and/or new lesions\]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Time frame: At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II)., but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).
Secondary
Percentage of Participants With Objective Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a \>=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by \>50% in length. The study was pre-maturely terminated at escalation phase.
Time frame: From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months
Population: The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II)., but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I).