Beta-Glucan and Rituximab in Treating Young Patients With Relapsed or Progressive Lymphoma or Leukemia, or Lymphoproliferative Disorder Related to Donor Stem Cell Transplantation
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Group I
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.
|
Given IV
Given orally
|
|
Experimental: Group II
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.
|
Given IV
Given orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
maximum tolerated dose
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
safety
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Nai-Kong V. Cheung, MD, PhD, Memorial Sloan Kettering Cancer Center
- Principal Investigator: Trudy N. Small, MD, Memorial Sloan Kettering Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- AIDS-related peripheral/systemic lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- post-transplant lymphoproliferative disorder
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood lymphoblastic lymphoma
- AIDS-related primary CNS lymphoma
Additional Relevant MeSH Terms
Other Study ID Numbers
- 03-095
- P30CA008748 (U.S. NIH Grant/Contract)
- MSKCC-03095
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