Leukemia, Lymphoma, Lymphoproliferative Disorder
Conditions
Keywords
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
Brief summary
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
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.
Interventions
BIOLOGICALbeta-glucan
Given orally
BIOLOGICALrituximab
Given IV
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| maximum tolerated dose | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| safety | 2 years |
Countries
United States
Outcome results
None listed