Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Obinutuzumab

Prednisone

Vincristine

Antineoplastic Agents, Immunological

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.

Ga101

Francesco Merli, MD

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

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.

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

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)

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.

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): patients in Partial Response after induction therapy.

Frequency of PRR already reported in the table of principal end-point.

ORR (Overall Response Rate): sum of patiens with Complete or Partial response after the induction therapy.

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): 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.

Change in Activities of daily living score. The score ranging from 0 (bad performance) to 6 (good performance)

Change in Instrumental Activities of Daily Living score. The score ranging from 0 (bad performance) to 8 (good performance).

Change in Cumulative Illness Rating Scale. The grading of comorbidity ranging from 0 (absent) to 4 (severe).

Fondazione Italiana Linfomi - ETS

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).

NOTE: One SAE (atrial fibrillation) was recorded in patient excluded from analysis (not eligible for transformed lymphoma), exit before starting the 1st cycle of treatment.

Single Arm

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)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Italy

Region of Enrollment

Hemoglobin

Ann Arbor Staging:

Stage I: nvolvement of a single lymph node region or lymphoid structure. Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm.

Stage III: Involvement of lymph regions or structures on both sides of the diaphragm.

Stage IV: Involvement of extranodal site(s) beyond that designated as an involvement of a single, extranodal site contiguous or proximal to known nodal site.

Bone marrow or liver involvement will always be considered as stage IV.

Stage

Bone Marrow Involvement

The presence of (a) unexplained weight loss of more than 10% of the body weight during the 6 months before initial staging investigation and/or (b) unexplained, persistent, or recurrent fever with temperatures above 38 C during the previous month and/or (c) recurrent drenching night sweats during the previous months is denoted by the suffix letter 'B'. 'A' indicates the absence of these symptoms

Symptoms

ECOG Performance Status grade:

0 Able to carry out all normal activity without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out light work
2. Ambulatory and capable of all self-care but unable to carry out any work; up and about more than50% of waking hours
3. Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any self-care; totally confined to bed or chair

ECOG PS (Eastern Cooperative Oncology Group Performance Status)

Ratio between measured level of LDH with the upper limit of normality. LDH levles with ratio \<=1 was considered normal, LDH levels with ratio \>1 was considered elevated.

LDH (lactate dehydrogenase)

International Prognostic Index (IPI): ranging fron 0 to 5. In this study was grouped 0-1 Low risk, 2 Intermediate risk, 3/5 High risk.

International Prognostic Index

Comprehensive Geriatric Assessment (CGA):

FIT patients, without any co-morbidity; UNFIT patients, with mild co-morbidities; FRAIL patients, with severe co-morbidities.

Comprehensive Geriatric Assessment

Dr. Luigi Marcheselli - FIL statistician

Patients who received at last 1 cycle of treatment

Complete Response Rate (CRR). Based a Central Independent Review Committee Considering Use the Conventional CT Scan Images.

Patients who received at least 1 cycle of treatment.

Adverse Events (AEs)

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) miniCHOP: an attenuated version of the standard CHOP, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Spots Global Cancer Trial Database for elderly unfit patients