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

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00087009

Purpose

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	Intervention	Phase
Leukemia Lymphoma Lymphoproliferative Disorder	Drug: beta-glucan Drug: rituximab	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Rituximab beta-Glucan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	24
Study Start Date:	May 2004
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group I: Experimental 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.	Drug: beta-glucan Given orally Drug: rituximab Given IV
Group II: Experimental 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.	Drug: beta-glucan Given orally Drug: rituximab Given IV

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087009

Locations

United States, New York
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

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000372422, MSKCC-03095
Study First Received:	July 8, 2004
Last Updated:	October 18, 2008
ClinicalTrials.gov Identifier:	NCT00087009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Leukemia, Lymphoid
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hodgkin's disease
Rituximab
Lymphoblastic lymphoma
Small non-cleaved cell lymphoma
Recurrence

Central nervous system lymphoma, primary
Post-transplant lymphoproliferative disease
Lymphoma, large-cell
Leukemia
Lymphatic Diseases
Hodgkin lymphoma, childhood
Lymphoproliferative Disorders
Lymphoma
Hodgkin Disease

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Disease
Immunologic Factors
Immune System Diseases

Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009