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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Terminated; Phase 1

Conditions: Lymphoproliferative Disorder; Lymphoma; Leukemia

Treatments: Biological: beta-glucan; Biological: rituximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00087009

03-095

P30CA008748 (U.S. NIH Grant/Contract)

MSKCC-03095

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Group I

Experimental group

Description:

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.

Treatment:

Biological: rituximab

Biological: beta-glucan

Group II

Experimental group

Description:

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.

Treatment:

Biological: rituximab

Biological: beta-glucan