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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


Phase 1
N/A
21 Years
Not Enrolling
Both
Leukemia, Lymphoma, Lymphoproliferative Disorder

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

maximum tolerated dose

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Shakeel Modak, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

03-095

NCT ID:

NCT00087009

Start Date:

May 2004

Completion Date:

August 2008

Related Keywords:

  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorder
  • 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
  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorders

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021