GA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma (FIL_GAEL)

Fondazione Italiana Linfomi - ETS

Status and phase: Terminated; Phase 2

Conditions: CD20 Positive Diffuse Large B-cell Lymphoma; Elderly Unfit Patients

Treatments: Drug: Ga101

Study type: Interventional

Funder types: Other

Identifiers

NCT02495454

2014-005697-10 (EudraCT Number)

FIL_GAEL

Details and patient eligibility

About

GA101-miniCHOP regimen for the treatment of elderly unfit patients with diffuse large B-cell non-Hodgkin's lymphoma.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Ga101-miniCHOP

Experimental group

Description:

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.

Treatment:

Drug: Ga101