Beta-Glucan and Rituximab in Treating Young Patients With Relapsed or Progressive Lymphoma or Leukemia, or Lymphoproliferative Disorder Related to Donor Stem Cell Transplantation

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Beta-glucan may increase the effectiveness of rituximab by making cancer cells more sensitive to the monoclonal antibody. PURPOSE: This phase I trial is studying the side effects and best dose of beta-glucan when given together with rituximab in treating young patients with relapsed or progressive lymphoma or leukemia or with lymphoproliferative disorder related to donor stem cell transplantation.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of beta-glucan when given in combination with rituximab in pediatric patients with relapsed or progressive CD20-positive lymphoma or leukemia or post-allogeneic stem cell transplant-related lymphoproliferative disorder. Determine the toxicity of this regimen, with special emphasis on the degree of B-cell depletion and immune suppression, in these patients. Determine the effects of beta-glucan on leukocyte-mediated cytotoxic effects in patients treated with this regimen. Secondary Determine the antitumor effect of this regimen in these patients. OUTLINE: This is a dose-escalation study of beta-glucan. Patients are assigned to 1 of 2 treatment groups according to diagnosis. Group I (lymphoma or leukemia): Patients receive rituximab IV on days 1, 8, 15, and 22 and oral beta-glucan once daily on days 1-28 (days 8-28 of course 1). Treatment repeats every 42 days for 4 courses in the absence of disease progression or unacceptable toxicity. Group II (post-allogeneic stem cell transplant-related lymphoproliferative disorder): Patients receive rituximab IV on days 1, 4, 8, 15, and 22 and oral beta-glucan once daily on days 8-28. Beginning on day 42, patients with responding disease may receive monthly rituximab prophylaxis until their CD4 cell count is > 200/mm^3. Cohorts of 6 patients receive escalating doses of beta-glucan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 2 years. PROJECTED ACCRUAL: A total of 6-24 patients will be accrued for this study within 2 years.

Official Title
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Phase I Study of Oral ß-Glucan and Intravenous Rituximab Among Children and Adolescents With Relapsed CD20-Positive Lymphoma or Leukemia, or Post-Transplant Lymphoproliferative Disease

Conditions
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Leukemia, Lymphoma, Lymphoproliferative Disorder

Intervention / Treatment
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* Biological: beta-glucan
* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: B-cell non-Hodgkin's lymphoma (NHL) Hodgkin's lymphoma Post-transplant lymphoproliferative disorder (PTLD) Lymphoblastic leukemia CD20-positive disease verified by immunophenotyping at original diagnosis, disease relapse, or disease progression Refractory to conventional therapy, defined as 1 of the following: Medically refractory HIV-associated NHL Refractory or recurrent lymphoblastic leukemia PTLD In > first relapse or progression of B-cell NHL or Hodgkin's lymphoma Measurable (CT scan or MRI) or evaluable (marrow metastases or circulating lymphoblasts) disease within 4 weeks after completion of prior systemic (including systemic steroids) therapy PATIENT CHARACTERISTICS: Age Under 22 Performance status Not specified Life expectancy Not specified Hematopoietic Absolute neutrophil count > 500/mm^3* Platelet count > 10,000/mm^3* NOTE: *Excluding patients with PTLD or CD20-positive lymphoblastic leukemia Hepatic Hepatic toxicity ≤ grade 2 Renal Creatinine clearance ≥ 60 mL/min Renal toxicity ≤ grade 2 Cardiovascular Cardiac toxicity ≤ grade 2 Pulmonary Pulmonary toxicity ≤ grade 2 Immunologic Human anti-mouse antibody (HAMA) ≤ 1,000 units/mL Human anti-chimeric antibody titer negative No active, life-threatening infections except Epstein-Barr virus-associated lymphoproliferative disorder No history of allergy to mouse proteins No history of allergy to rituximab or other chimeric monoclonal antibodies No history of allergy to beta-glucan or oats, barley, mushrooms, or yeast Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Grade 3 hearing deficit allowed Gastrointestinal toxicity ≤ grade 2 Neurologic toxicity ≤ grade 2 No severe major organ toxicity PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics More than 4 weeks since prior rituximab No prior mouse antibodies No prior chimeric antibodies Chemotherapy Not specified Endocrine therapy See Disease Characteristics Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Maximum Age: 21 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>Patients receive rituximab IV on days 1, 8, 15, and 22 and oral beta-glucan once daily on days 1-28 (days 8-28 of course 1). Treatment repeats every 42 days for 4 courses. | Biological: beta-glucan<br>* Given orally<br>Biological: rituximab<br>* Given IV<br>|
| Experimental: Group II<br>Patients receive rituximab IV on days 1, 4, 8, 15, and 22 and oral beta-glucan once daily on days 8-28. Beginning on day 42, patients with responding disease may receive monthly rituximab prophylaxis. | Biological: beta-glucan<br>* Given orally<br>Biological: rituximab<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-transplant lymphoproliferative disorder, recurrent childhood acute lymphoblastic leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma