Clinical trial NCT02495454: GA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: CD20 Positive Diffuse Large B-cell Lymphoma
Elderly Unfit Patients
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2015-07-13
Enrollment: 34
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.
timeFrame: Up to 36 months.
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to 36 months
measure: Partial Response Rate (PRR)
timeFrame: Up to 36 months
measure: ORR (Overall Response Rate)
timeFrame: Up to 36 months
measure: OS (Overall Survival)
timeFrame: Up to 36 months
measure: PFS (Progression Free Survival)
timeFrame: Up to 36 months
measure: Activities of Daily Living (ADL)
timeFrame: Up to 36 months
measure: Instrumental Activities of Daily Living (IADL)
timeFrame: Up to 36 months
measure: Cumulative Illness Rating Scale (CIRS)
timeFrame: Up to 36 months
measure: Questionnaire for Quality of Life (EORTC QLQ C30)
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: A.O. Spedali Civili
state: BS
city: Ravenna
country: Italy
facility: AUSL di Ravenna
state: RA
city: Reggio Emilia
country: Italy
facility: Asmn-Irccs
state: RE
city: Torino
country: Italy
facility: Ematologia 1U - AO Città della Salute e della Scienza
state: TO
city: Terni
country: Italy
facility: A.O. S. Maria di Terni
state: TR
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e C. Arrigo
city: Ancona
country: Italy
facility: A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
city: Biella
country: Italy
facility: A.O. Ospedale Degli Infermi
city: Meldola (FC)
country: Italy
facility: Area Vasta Romagna e IRST
city: Milano
country: Italy
facility: IRCCS, Istituto Nazionale dei Tumori
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena
city: Novara
country: Italy
facility: SCDU Ematologia - Università del Piemonte Orientale
city: Padova
country: Italy
facility: Irccs Istituto Oncologico Veneto (Iov)
city: Palermo
country: Italy
facility: Oncoematologia e TMO Dopartimento Oncologia La Maddalena
city: Rimini
country: Italy
facility: Ausl Di Rimini
city: Varese
country: Italy
facility: Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
Study officials:
affiliation: Ematologia - IRCCS Arcispedale Santa Maria Nuova
name: Francesco Merli, MD
role: PRINCIPAL_INVESTIGATOR
References: