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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Terminated

CT.gov ID

NCT00087009

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Lymphoproliferative Disorder	Biological: beta-glucan Biological: rituximab	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Aug 1, 2008

Arms and Interventions

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

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.

Biological: beta-glucan

Given orally

Biological: rituximab

Given IV

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.

Biological: beta-glucan

Given orally

Biological: rituximab

Given IV

Outcome Measures

Primary Outcome Measures

maximum tolerated dose [2 years]

Secondary Outcome Measures

safety [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)

Investigators

Principal Investigator: Shakeel Modak, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Nai-Kong V. Cheung, MD, PhD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Trudy N. Small, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Tanya Trippett, MD, Memorial Sloan Kettering Cancer Center