Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with liposomal doxorubicin may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects of giving rituximab together with liposomal doxorubicin and to see how well they work in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the safety, including qualitative and quantitative toxic effects and their duration and reversibility, of rituximab and doxorubicin HCl liposome in patients with relapsed or refractory, indolent or aggressive CD20-positive B-cell non-Hodgkin's lymphoma. Secondary Determine the efficacy, including overall response rate and durability of objective response, of this regimen in these patients. Correlate pretreatment functional, phenotypic, and genotypic characteristics of host immune effector cells with response in patients treated with this regimen. OUTLINE: This is an open-label, pilot study. Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 4 years. PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Official Title
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A Phase I/II Pilot Study of the Safety and Efficacy of Rituxan (Chimeric Anti-CD20 Antibody) in Combination With Doxil (Liposomal Doxorubicin) Chemotherapy in Patients With Relapsing or Refractory Indolent or Aggressive B-Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: pegylated liposomal doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL) subtypes: Grade 1-3 follicular lymphoma Mantle cell lymphoma Small lymphocytic lymphoma Diffuse large B-cell lymphoma Diffuse mixed cell lymphoma Marginal zone lymphoma Relapsed or refractory CD20-positive disease Measurable disease Must have received ≥ 1 but < 4 prior standard chemotherapy regimens No Burkitt's lymphoma or precursor B-lymphoblastic lymphoma No CNS lymphoma PATIENT CHARACTERISTICS: Performance status Karnofsky 60-100% Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin > 7 g/dL Hepatic AST or ALT < 2 times upper limit of normal (unless due to primary disease) Bilirubin ≤ 2 mg/dL Renal Creatinine ≤ 2.0 mg/dL Cardiovascular LVEF ≥ 50% by MUGA and/or 2-D echocardiogram No history of New York Heart Association class II-IV cardiac disease No congestive heart failure Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity No uncontrolled active bacterial, viral, or fungal infection No other serious disease that would preclude study participation No other primary malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Recovered from prior immunotherapy Prior immunotherapy, including rituximab or other monoclonal antibody, allowed Chemotherapy See Disease Characteristics More than 4 weeks since prior chemotherapy and recovered No prior doxorubicin (or equivalent anthracycline) at a cumulative dose > 400 mg/m^2 No other concurrent chemotherapy Endocrine therapy Nonsteroidal hormones for nonlymphoma-related conditions (e.g., insulin for diabetes) allowed No concurrent corticosteroids except for a transient inflammatory reaction (i.e., skin rash or hives) Radiotherapy Recovered from prior radiotherapy No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery (other than diagnostic surgery) and recovered Other No other concurrent antitumor agents No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Rituximab and Doxorubicin HCI Liposome<br>Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3 | Biological: rituximab<br>* IV<br>Drug: pegylated liposomal doxorubicin hydrochloride<br>* IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate at 20 Weeks | Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 em before therapy). Previously involved nodes that were 1.1 to 1.5 in their greatest transverse diameter before treatment must have decreased to 1 cm in their greatest transverse diameter after treatment or by more than 75% in the sum of the products of the greatest diameters (SPD). The patient must also be free from symptoms related to lymphoma, if present before therapy with no worsening in performance status from baseline. Bone marrow, if initially positive at baseline, must be histologically negative for lymphoma and the liver and spleen, if enlarged due to lymphoma at baseline, should be normalized. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Response Rate at 20 Weeks | Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted. | 20 weeks | 
| Overall Response Rate (Complete and Partial Responses) at 20 Weeks | Complete Response (CR): During observation no disease is apparent, including measurable and non-measurable disease, for at least 28 days, as confirmed by a second assessment following the original observation of no disease. All nodes visualized on imaging studies or palpable on exams must have regressed to normal size their greatest transverse diameter for nodes > 1.5 before therapy. Partial Response (PR): A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the > or = to 50% decrease. Additionally, no appearance of new lesions is noted. | 20 weeks | 
| Progression Free Survival (PFS) Rate at 2 Years | Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions. | 2 years | 
| Overall Survival (OS) Rate at 2 Years | Overall survival was defined as time from date of treatment initiation until date of death due to any cause. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent small lymphocytic lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma