GA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma A Phase II Study of the Fondazione Italiana Linfomi (FIL)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 34
- Locations
- 16
- Primary Endpoint
- Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically proven CD20 positive Diffuse Large B-cell Lymphoma and Follicular grade III B lymphoma, according to WHO (World Health Organization) classification (local pathologist)
- •Age ≥ 65 years
- •No previous treatment
- •CGA assessment (Comprehensive Geriatric Assessment) performed before starting treatment
- •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
- •Ann Arbor Stage I with bulky, II-IV
- •At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
- •ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2
- •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
- •LVEF (Left Ventricular Ejection Fraction) >50%
- •Ability and willingness to comply with the study protocol procedure
- •Life expectancy > 6 months
- •Accessibility of patient for treatment and follow up
- •Written informed consent
Exclusion Criteria
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- •Contraindication to any of the individual components of CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), including prior receipt of anthracyclines
- •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
- •Stage I without bulky
- •Patients with transformed lymphoma
- •Prior therapy for DLBCL (Diffuse Large B Cell Lymphoma), with the exception of nodal biopsy or local irradiation
- •Previous exposure to cytotoxic agents
- •Suspect or clinical evidence of CNS (Central Nervous System) involvement by lymphoma
- •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
- •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)
- •Evidence of any severe active acute or chronic infection
- •Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy
Arms & Interventions
Ga101-miniCHOP
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).
GA101-miniCHOP regimen:
- Cycle 1 GA101: 1000 mg day 1, day 8 and day 15, iv Cyclophosphamide: 400 mg/mq, day 1, iv Doxorubicin: 25 mg/mq, day 1, iv Vincristine: 1 mg, day 1, iv Prednisone: 40 mg/mq, days 1-5, os
- Cycles 2-6 GA101: 1000 mg day 1, iv Cyclophosphamide: 400 mg/mq, day 1, iv Doxorubicin: 25 mg/mq, day 1, iv Vincristine: 1 mg, day 1, iv Prednisone: 40 mg/mq, days 1-5, os
- Two additional infusions of GA101: 1000 mg day 1, iv, every 21 days.
Intervention: Ga101 (Drug)
Outcomes
Primary Outcomes
Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.
Time Frame: 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 Outcomes
- ORR (Overall Response Rate)(Up to 36 months)
- Instrumental Activities of Daily Living (IADL)(Up to 36 months)
- Cumulative Illness Rating Scale (CIRS)(Up to 36 months)
- Questionnaire for Quality of Life (EORTC QLQ C30)(Up to 36 months)
- Adverse Events (AEs)(Up to 36 months)
- Partial Response Rate (PRR)(Up to 36 months)
- OS (Overall Survival)(Up to 36 months)
- PFS (Progression Free Survival)(Up to 36 months)
- Activities of Daily Living (ADL)(Up to 36 months)