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

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)

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

Study Overview

• Status: Terminated
• Conditions: CD20 Positive Diffuse Large B-cell Lymphoma; Elderly Unfit Patients
• Intervention / Treatment: Drug: Ga101

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • A.O. SS. Antonio e Biagio e C. Arrigo
  • Ancona, Italy, 60126
    • A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
  • Biella, Italy, 13900
    • A.O. Ospedale Degli Infermi
  • Meldola (FC), Italy
    • Area Vasta Romagna e IRST
  • Milano, Italy
    • IRCCS, Istituto Nazionale dei Tumori
  • Modena, Italy, 41124
    • A.O. Universitaria Policlinico Di Modena
  • Novara, Italy, 28100
    • SCDU Ematologia - Università del Piemonte Orientale
  • Padova, Italy, 35128
    • IRCCS Istituto Oncologico Veneto (IOV)
  • Palermo, Italy
    • Oncoematologia e TMO Dopartimento Oncologia La Maddalena
  • Rimini, Italy, 47924
    • Ausl Di Rimini
  • Varese, Italy, 21100
    • Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
  • BS
    • Brescia, BS, Italy, 25100
      • A.O. Spedali Civili
  • RA
    • Ravenna, RA, Italy, 48100
      • AUSL di Ravenna
  • RE
    • Reggio Emilia, RE, Italy, 43123
      • Asmn-Irccs
  • TO
    • Torino, TO, Italy, 10126
      • Ematologia 1U - AO Città della Salute e della Scienza
  • TR
    • Terni, TR, Italy, 05100
      • A.O. S. Maria di Terni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Ga101; Other Names: Obinutuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 36 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 36 months
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.	Up to 36 months
ORR (Overall Response Rate)	ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy.	Up to 36 months
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.	Up to 36 months
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.	Up to 36 months
Activities of Daily Living (ADL)	Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance)	Up to 36 months
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).	Up to 36 months
Cumulative Illness Rating Scale (CIRS)	Change in Cumulative Illness Rating Scale. The grading of comorbidity ranging from 0 (absent) to 4 (severe).	Up to 36 months
Questionnaire for Quality of Life (EORTC QLQ C30)	Change in quality of life (QoL)	Up to 36 months

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi ONLUS
• Investigators: Principal Investigator: Francesco Merli, MD, Ematologia - IRCCS Arcispedale Santa Maria Nuova

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2015
• Primary Completion (Actual): March 22, 2017
• Study Completion (Actual): March 22, 2017

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: July 8, 2015
• First Posted (Estimate): July 13, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: FIL_GAEL; 2014-005697-10 (EudraCT Number)