CD20 Positive Diffuse Large B-cell Lymphoma, Elderly Unfit Patients
Conditions
Brief summary
GA101-miniCHOP regimen for the treatment of elderly unfit patients with diffuse large B-cell non-Hodgkin's lymphoma.
Detailed description
Considering that the treatment of elderly unfit patients with DLBCL cannot be based on a full course of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), and that using a less intense R-miniCHOP (an attenuated version of the standard R-CHOP: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) combination an acceptable cure rate can be achieved this study is designed to try to improve the cure rate in unfit patients with DLBCL (Diffuse Large B Cell Lymphoma) by adopting the R-miniCHOP scheme substituting Rituximab with the more active GA101 monoclonal antibody. The study hypothesis is that a higher activity of the treatment can be achieved without modifying the cytotoxic part of the treatment but using a more active immunotherapy. Differently from the previous experience with R-miniCHOP eligible patient are not only identified using anagraphic criteria but adopting CGA (Comprehensive Geriatric Assessment) as part of initial assessment and considering as eligible unfit patients.
Interventions
DRUGGa101
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically proven CD20 positive Diffuse Large B-cell Lymphoma and Follicular grade III B lymphoma, according to WHO (World Health Organization) classification (local pathologist) 2. Age ≥ 65 years 3. No previous treatment 4. CGA assessment (Comprehensive Geriatric Assessment) performed before starting treatment 5. Unfit patients defined as follows: Age \> 80 years with Fit profile, i.e. ADL (Activity of Daily Living) =6 residual functions IADL (Instrumental Activity of Daily Living) =8 residual functions CIRS (Cumulative Illness Rating Scale): no comorbidity of grade 3-4 and \<5 of grade 2 or Age \< 80 with Unfit profile, i.e ADL(Activity of Daily Living) \> 5 residual functions IADL (Instrumental Activity of Daily Living) \> 6 residual functions CIRS (Cumulative Illness Rating Scale): no comorbidity of grade 3-4 and 5-8 co-morbidities of grade 2 6. Ann Arbor Stage I with bulky, II-IV 7. At least one bi-dimensionally measurable lesion defined as \> 1.5 cm in its largest dimension on CT scan 8. ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 9. Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows: Hemoglobin ≥ 10 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L 10. LVEF (Left Ventricular Ejection Fraction) \>50% 11. Ability and willingness to comply with the study protocol procedure 12. Life expectancy \> 6 months 13. Accessibility of patient for treatment and follow up 14. Written informed consent
Exclusion criteria
1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 2. Contraindication to any of the individual components of CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), including prior receipt of anthracyclines 3. History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer 4. Stage I without bulky 5. Patients with transformed lymphoma 6. Prior therapy for DLBCL (Diffuse Large B Cell Lymphoma), with the exception of nodal biopsy or local irradiation 7. Previous exposure to cytotoxic agents 8. Suspect or clinical evidence of CNS (Central Nervous System) involvement by lymphoma 9. HBsAg (Hepatitis B surface antigen), HCV (Hepatitis C Virus) or HIV (Human Immunodeficiency Virus) positivity; isolated HBcAb (Hepatitis B surface antibody) positivity is accepted only with concomitant treatment with Lamivudine 10. AST /ALT (Aspartate Aminotransferase/Alanine Aminotransferase)\> twice upper the normal range; bilirubin \> twice upper the normal range; serum creatinine \> 2.5 mg /dl (unless these abnormalities were related to the lymphoma) 11. Evidence of any severe active acute or chronic infection 12. Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Up to 36 months. | Complete Response Rate after 10 infusions of GA101 and 6 cycles of miniCHOP. Complete Remission (CR): Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, normalization of biochemistry abnormalities. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site. Partial disease (PR): \>= 50% decrease in node diameter of the six largest dominant nodes or nodal masses and no new sites of disease; Stable disease (SD): is defined as less than a PR but is not progressive disease. Progession disease (PD): \>50% increase diameter of node from nadir of any previously identified abnormal node nonresponders, and/or appearance of any new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Response Rate (PRR) | Up to 36 months | Partial Response Rate (PRR): patients in Partial Response after induction therapy. Frequency of PRR already reported in the table of principal end-point. |
| ORR (Overall Response Rate) | Up to 36 months | ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy. |
| OS (Overall Survival) | Up to 36 months | OS (Overall Survival): defined as the time from the date of treatment start into the study until the date of death irrespective of cause. Patients who have not died at the time of end of the whole study, and patients who are lost to follow up, will be censored at the date of the last contact. |
| PFS (Progression Free Survival) | Up to 36 months | PFS (Progression Free Survival): defined as the time from entry into the study until lymphoma relapse/ progression or death as a result of any cause. Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date. |
| Adverse Events (AEs) | Up to 36 months | Rate of Adverse Events. Although was not defined a formal threshold, in this section we reported the summary of frequencies of maximum CTCAE observed in patients. Each patient was counted only once within the AE terms during the therapy. If, during the therapy the patient experiences more than one AE, only the AE with the greatest intensity was included in the summary. |
| Instrumental Activities of Daily Living (IADL) | Up to 36 months | Change in Instrumental Activities of Daily Living score. The score ranging from 0 (bad performance) to 8 (good performance). |
| Cumulative Illness Rating Scale (CIRS) | Up to 36 months | Change in Cumulative Illness Rating Scale. The grading of comorbidity ranging from 0 (absent) to 4 (severe). |
| Questionnaire for Quality of Life (EORTC QLQ C30) | Up to 36 months | Change in quality of life (QoL) |
| Activities of Daily Living (ADL) | Up to 36 months | Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance) |
Countries
Italy
Participant flow
Pre-assignment details
One case excluded for violation of inclusion criteria (transformed lymphoma)
Participants by arm
| Arm | Count |
|---|---|
| Single Arm 6 courses of GA101-miniCHOP regimen and 2 additional infusions of GA101, every 21 days (for a total of 6 courses of miniCHOP and 10 infusions of GA101) | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 82 years |
| Bone Marrow Involvement Negative | 27 Participants |
| Bone Marrow Involvement Positive | 6 Participants |
| Comprehensive Geriatric Assessment FRAIL | 5 Participants |
| Comprehensive Geriatric Assessment UNFIT | 28 Participants |
| ECOG PS (Eastern Cooperative Oncology Group Performance Status) 0 | 12 Participants |
| ECOG PS (Eastern Cooperative Oncology Group Performance Status) 1 | 19 Participants |
| ECOG PS (Eastern Cooperative Oncology Group Performance Status) 2-3 | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hemoglobin | 12.9 g/dL |
| International Prognostic Index 0-1 | 4 Participants |
| International Prognostic Index 2 | 8 Participants |
| International Prognostic Index 3/5 | 21 Participants |
| LDH (lactate dehydrogenase) <= Upper Limit | 10 Participants |
| LDH (lactate dehydrogenase) > Upper Limit | 23 Participants |
| Region of Enrollment Italy | 33 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 18 Participants |
| Stage II | 6 Participants |
| Stage III | 11 Participants |
| Stage IV | 16 Participants |
| Symptoms Absence of symptoms | 27 Participants |
| Symptoms Presence of symptoms | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 33 |
| other Total, other adverse events | 30 / 33 |
| serious Total, serious adverse events | 6 / 33 |
Outcome results
Primary
Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.
Complete Response Rate after 10 infusions of GA101 and 6 cycles of miniCHOP. Complete Remission (CR): Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, normalization of biochemistry abnormalities. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site. Partial disease (PR): \>= 50% decrease in node diameter of the six largest dominant nodes or nodal masses and no new sites of disease; Stable disease (SD): is defined as less than a PR but is not progressive disease. Progession disease (PD): \>50% increase diameter of node from nadir of any previously identified abnormal node nonresponders, and/or appearance of any new lesion.
Time frame: Up to 36 months.
Population: Patients who received at last 1 cycle of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Complete Response | 14 Participants |
| Single Arm | Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Partial Response | 8 Participants |
| Single Arm | Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Stable Disease | 2 Participants |
| Single Arm | Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Progression Disease | 8 Participants |
| Single Arm | Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images. | Not Assessed | 1 Participants |
Secondary
Activities of Daily Living (ADL)
Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance)
Time frame: Up to 36 months
Secondary
Adverse Events (AEs)
Rate of Adverse Events. Although was not defined a formal threshold, in this section we reported the summary of frequencies of maximum CTCAE observed in patients. Each patient was counted only once within the AE terms during the therapy. If, during the therapy the patient experiences more than one AE, only the AE with the greatest intensity was included in the summary.
Time frame: Up to 36 months
Population: Patients who received at least 1 cycle of treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Adverse Events (AEs) | CTCAE Grade 0 | 5 Participants |
| Single Arm | Adverse Events (AEs) | CTCAE grade 1-2 | 11 Participants |
| Single Arm | Adverse Events (AEs) | CTCAE grade >2 | 17 Participants |
Secondary
Cumulative Illness Rating Scale (CIRS)
Change in Cumulative Illness Rating Scale. The grading of comorbidity ranging from 0 (absent) to 4 (severe).
Time frame: Up to 36 months
Secondary
Instrumental Activities of Daily Living (IADL)
Change in Instrumental Activities of Daily Living score. The score ranging from 0 (bad performance) to 8 (good performance).
Time frame: Up to 36 months
Secondary
ORR (Overall Response Rate)
ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy.
Time frame: Up to 36 months
Population: Patients who received at leat 1 cycle of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | ORR (Overall Response Rate) | ORR | 22 Participants |
| Single Arm | ORR (Overall Response Rate) | Less than ORR | 11 Participants |
Secondary
OS (Overall Survival)
OS (Overall Survival): defined as the time from the date of treatment start into the study until the date of death irrespective of cause. Patients who have not died at the time of end of the whole study, and patients who are lost to follow up, will be censored at the date of the last contact.
Time frame: Up to 36 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm | OS (Overall Survival) | 0.69 Probability at 24 months |
Secondary
Partial Response Rate (PRR)
Partial Response Rate (PRR): patients in Partial Response after induction therapy. Frequency of PRR already reported in the table of principal end-point.
Time frame: Up to 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | Partial Response Rate (PRR) | Partial Remission | 8 Participants |
| Single Arm | Partial Response Rate (PRR) | Not in partial remission | 25 Participants |
Secondary
PFS (Progression Free Survival)
PFS (Progression Free Survival): defined as the time from entry into the study until lymphoma relapse/ progression or death as a result of any cause. Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date.
Time frame: Up to 36 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm | PFS (Progression Free Survival) | 0.53 Probability at 24 months |
Secondary
Questionnaire for Quality of Life (EORTC QLQ C30)
Change in quality of life (QoL)
Time frame: Up to 36 months