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

March 18, 2013 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: rituximab
Given IV
Biological: beta-glucan
Given orally
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: rituximab
Given IV
Biological: beta-glucan
Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
maximum tolerated dose
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
safety
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

July 8, 2004

First Submitted That Met QC Criteria

July 9, 2004

First Posted (Estimate)

July 12, 2004

Study Record Updates

Last Update Posted (Estimate)

March 19, 2013

Last Update Submitted That Met QC Criteria

March 18, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-095
  • P30CA008748 (U.S. NIH Grant/Contract)
  • MSKCC-03095

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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