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
N/A
21 Years
Both
Leukemia, Lymphoma, Lymphoproliferative Disorder
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
maximum tolerated dose
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Shakeel Modak, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
03-095
NCT ID:
NCT00087009
Start Date:
May 2004
Completion Date:
August 2008
Related Keywords:
- Leukemia
- Lymphoma
- Lymphoproliferative Disorder
- 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
- Leukemia
- Lymphoma
- Lymphoproliferative Disorders
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
