Back to resultsGA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma (FIL_GAEL)
Primary Purpose
CD20 Positive Diffuse Large B-cell Lymphoma, Elderly Unfit Patients
Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Ga101
Sponsored by
About this trial
This is an interventional treatment trial for CD20 Positive Diffuse Large B-cell Lymphoma
Eligibility Criteria
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
Sites / Locations
- A.O. Spedali Civili
- AUSL di Ravenna
- Asmn-Irccs
- Ematologia 1U - AO Città della Salute e della Scienza
- A.O. S. Maria di Terni
- A.O. SS. Antonio e Biagio e C. Arrigo
- A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
- A.O. Ospedale Degli Infermi
- Area Vasta Romagna e IRST
- IRCCS, Istituto Nazionale dei Tumori
- A.O. Universitaria Policlinico Di Modena
- SCDU Ematologia - Università del Piemonte Orientale
- Irccs Istituto Oncologico Veneto (Iov)
- Oncoematologia e TMO Dopartimento Oncologia La Maddalena
- Ausl Di Rimini
- Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ga101-miniCHOP
Arm 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
ORR (Overall Response Rate)
ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy.
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.
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.
Activities of Daily Living (ADL)
Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance)
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).
Cumulative Illness Rating Scale (CIRS)
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)
Change in quality of life (QoL)
Full Information
NCT ID
NCT02495454
First Posted
June 8, 2015
Last Updated
November 4, 2020
Sponsor
Fondazione Italiana Linfomi - ETS
1. Study Identification
Unique Protocol Identification Number
NCT02495454
Brief Title
GA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma
Acronym
FIL_GAEL
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
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Terminated
Why Stopped
Primary objective not obtained after interim analysis
Study Start Date
August 25, 2015 (Actual)
Primary Completion Date
March 22, 2017 (Actual)
Study Completion Date
March 22, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Italiana Linfomi - ETS
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CD20 Positive Diffuse Large B-cell Lymphoma, Elderly Unfit Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ga101-miniCHOP
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Ga101
Other Intervention Name(s)
Obinutuzumab
Primary Outcome Measure Information:
Title
Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.
Description
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.
Secondary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
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
Title
Partial Response Rate (PRR)
Description
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
Title
ORR (Overall Response Rate)
Description
ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy.
Time Frame
Up to 36 months
Title
OS (Overall Survival)
Description
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
Title
PFS (Progression Free Survival)
Description
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
Title
Activities of Daily Living (ADL)
Description
Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance)
Time Frame
Up to 36 months
Title
Instrumental Activities of Daily Living (IADL)
Description
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
Title
Cumulative Illness Rating Scale (CIRS)
Description
Change in Cumulative Illness Rating Scale. The grading of comorbidity ranging from 0 (absent) to 4 (severe).
Time Frame
Up to 36 months
Title
Questionnaire for Quality of Life (EORTC QLQ C30)
Description
Change in quality of life (QoL)
Time Frame
Up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Merli, MD
Organizational Affiliation
Ematologia - IRCCS Arcispedale Santa Maria Nuova
Official's Role
Principal Investigator
Facility Information:
Facility Name
A.O. Spedali Civili
City
Brescia
State/Province
BS
ZIP/Postal Code
25100
Country
Italy
Facility Name
AUSL di Ravenna
City
Ravenna
State/Province
RA
ZIP/Postal Code
48100
Country
Italy
Facility Name
Asmn-Irccs
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
43123
Country
Italy
Facility Name
Ematologia 1U - AO Città della Salute e della Scienza
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
A.O. S. Maria di Terni
City
Terni
State/Province
TR
ZIP/Postal Code
05100
Country
Italy
Facility Name
A.O. SS. Antonio e Biagio e C. Arrigo
City
Alessandria
ZIP/Postal Code
15121
Country
Italy
Facility Name
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
City
Ancona
ZIP/Postal Code
60126
Country
Italy
Facility Name
A.O. Ospedale Degli Infermi
City
Biella
ZIP/Postal Code
13900
Country
Italy
Facility Name
Area Vasta Romagna e IRST
City
Meldola (FC)
Country
Italy
Facility Name
IRCCS, Istituto Nazionale dei Tumori
City
Milano
Country
Italy
Facility Name
A.O. Universitaria Policlinico Di Modena
City
Modena
ZIP/Postal Code
41124
Country
Italy
Facility Name
SCDU Ematologia - Università del Piemonte Orientale
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Irccs Istituto Oncologico Veneto (Iov)
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Oncoematologia e TMO Dopartimento Oncologia La Maddalena
City
Palermo
Country
Italy
Facility Name
Ausl Di Rimini
City
Rimini
ZIP/Postal Code
47924
Country
Italy
Facility Name
Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
City
Varese
ZIP/Postal Code
21100
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
GA101-miniCHOP Regimen for the Treatment of Elderly Unfit Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma
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