Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of LR-CHOP21 for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma

Study Overview
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Brief Summary
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This is a prospective multicenter phase II pilot trial designed with the purpose of dose finding to evaluate the efficacy and safety of treatment with Lenalidomide plus R-CHOP21 (LR-CHOP21) for elderly patients with untreated Diffuse Large B Cell Lymphoma (DLBCL).

Official Title
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Prospective Multicenter Dose Finding Phase II Pilot Trial to Evaluate Efficacy and Safety of Treatment With Lenalidomide Plus R-CHOP21 (LR-CHOP21) for Elderly Patients With Untreated Diffuse Large B Cell Lymphoma (DLBCL)

Conditions
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Non Hodgkin Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Drug: LR-CHOP21


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign an informed consent form Able to adhere to the study visit schedule and other protocol requirements Histologic subtypes as follows: CD20 positive Diffuse large B-Cell lymphoma CD20 positive Follicular grade IIIb Age 60-80 Untreated patients. In patients with bulky mass or systemic symptoms or compressive disease or rapidly progressive adenopathies a pre-study treatment is allowed with steroids and/or a single dose of Vincristine 1.4 mg/mq (max 2) in the seven days prior the start of the study treatment Measurable and/or evaluable disease Ann Arbor stage II, III, IV International Prognostic Index at low-intermediate, intermediate-high, high risk (2/3/4-5) Adequate haematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L unless due to bone marrow involvement Conjugated bilirubin up to 2 x UNL Alkaline phosphatase and transaminases up to 2 x UNL Creatinine clearance > 50 ml/min HIV negativity HCV negativity HBV negativity or patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative Cardiac ejection fraction (MUGA scan or echocardiography) > 45% Non peripheral neuropathy or CNS disease. Non testicular Lymphoma Life expectancy > 6 months Performance status < 2 according to ECOG scale Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing absence of any impairment in activity of daily living (ADL), of any condition defining a geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3 comorbidities according to CIRS-G scale Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: for at least 28 days before starting study drug;while participating in the study; for at least 28 days after discontinuation from the study The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, cervical cap) FCBP must be referred to a qualified provider of contraceptive methods if needed Exclusion Criteria: Lymphoblastic Lymphoma Burkitt Lymphoma Non Hodgkin lymphoma CD 20 negative Mantle Cell Lymphoma Follicular Non Hodgkin Lymphoma grade I-II-IIIa Primitive mediastinal diffuse large B cell lymphoma with only mediastinal involvement International Prognostic Index at low risk (1) Has known or suspected hypersensitivity or intolerance to Rituximab History of evolutive malignancy within the last 3 years other than squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast Extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy before enrollment within 3 years before the start of treatment Exposure to Rituximab prior to study entry Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study CNS disease (meningeal and/or brain involvement by lymphoma) or Testicular involvement DVT in the last year History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis Creatinine clearance < 50 ml/min Presence of major neurological disorders HIV positivity HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative HCV positivity Active opportunistic infection Comprehensive geriatric assessment (CGA) as outlined in Appendix 15 showing presence of any impairment in activity of daily living (ADL), of any condition defining a geriatric syndrome, and of any grade 4 comorbidity or of more than three grade 3 comorbidities according to CIRS-G scale Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohorts 1 - 2 - 3 - 4<br>Chemiotherapy | Drug: LR-CHOP21<br>* FIRST DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 5 mg/day D1-D14 SECOND DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1;Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 10 mg/day D1-D14 THIRD DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 15 mg/day D1-D14 FOURTH DOSE LEVEL: Rituximab 375 mg/sqm D 0 or 1; Cyclophosphamide 750 mg/sqm iv D1; Doxorubicin 50 mg/sqm iv D1; Vincristine 1.4 mg/sqm iv D1; Prednisone 40 mg/sqm orally D1, D2, D3, D4, D5; Revlimid 20 mg/day D1-D14 Repeated every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of adverse events according with Common Terminology Criteria for Adverse events (CTCAE) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Non Hodgkin Lymphoma, Follicular Lymphoma