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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00087009
• Other study ID #: 03-095
• Secondary ID: P30CA008748MSKCC
• Status: Terminated
• Phase: Phase 1
• First received: July 8, 2004
• Last updated: March 18, 2013
• Start date: May 2004
• Est. completion date: August 2008

Study information

• Verified date: March 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders

Intervention

Biological:
• beta-glucan
Given orally
• rituximab
Given IV

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose		2 years	No
Secondary	safety		2 years	Yes