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

NCT ID: NCT00087009

Last Updated: 2013-03-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2008-08-31

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.

Conditions

Leukemia; Lymphoma; Lymphoproliferative Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

beta-glucan

Intervention Type: BIOLOGICAL

Given orally

rituximab

Intervention Type: BIOLOGICAL

Given IV

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.

Group Type: EXPERIMENTAL

beta-glucan

Intervention Type: BIOLOGICAL

Given orally

rituximab

Intervention Type: BIOLOGICAL

Given IV

Interventions

beta-glucan

Given orally

Intervention Type: BIOLOGICAL

rituximab

Given IV

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shakeel Modak, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Nai-Kong V. Cheung, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Trudy N. Small, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Tanya Trippett, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-03095

Identifier Type: -

Identifier Source: secondary_id

03-095

Identifier Type: -

Identifier Source: org_study_id