Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma

Trial Information

A Phase I Study of Flavopiridol, Fludarabine and Rituximab in Indolent B-cell Lymphoproliferative Disorders and Mantle Cell Lymphoma

PRIMARY OBJECTIVES:

I. To determine a safe and tolerated dose of flavopiridol (alvocidib) in combination with
standard dose rituximab and fludarabine (fludarabine phosphate) in patients with indolent
B-cell lymphoproliferative disorders and mantle cell lymphoma.

II. To assess the toxicity of the combination regimen of flavopiridol, rituximab and
fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell
lymphoma.

III. To determine the safety, toxicity and efficacy of administering flavopiridol as a
30-minute bolus followed by 4-hour infusion, in combination with rituximab and fludarabine
in patients with indolent B-cell lymphoproliferative disorders and mantle cell lymphoma.

SECONDARY OBJECTIVES:

I. To determine pharmacokinetics of the combination regimen of flavopiridol, rituximab and
fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell
lymphoma.

II. To determine pharmacodynamics of the combination regimen of flavopiridol, rituximab and
fludarabine in patients with indolent B-cell lymphoproliferative disorders and mantle cell
lymphoma.

OUTLINE: This is a dose-escalation study of alvocidib.

Patients receive fludarabine phosphate intravenously (IV) over 15-30 minutes on days 1-5 and
rituximab IV over 3-4 hours on day 1. Alvocidib is administered IV over 60 minutes on day 1
in cohort 1; on days 1 and 2 in cohort 2; and on days 1, 2, and 3 in cohort 3. In cohorts 4
and 5, patients receive fludarabine phosphate and rituximab as above and alvocidib IV over
30 minutes and then IV over 4 hours on day 1 of courses 2-6. Treatment repeats every 28 days
for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Inclusion Criteria:

- Histologically confirmed mantle cell lymphoma OR indolent B-cell lymphoproliferative
disorders of any of the following types:

- Chronic lymphocytic leukemia

- Small lymphocytic lymphoma

- Follicular center cell non-Hodgkin's lymphoma (grade I or II)

- Marginal zone lymphoma

- Waldenstrom's macroglobulinemia

- Hairy cell leukemia

- Previously untreated or relapsed/refractory disease

- No evidence of histological transformation to an intermediate-grade or aggressive
lymphoma

- CD20 positive by immunoperoxidase or flow cytometry

- Evaluable disease with presence of 1 of the following criteria:

- Absolute lymphocyte count greater than 5,000/mm^3

- At least 1 measurable node greater than 2 cm by computed tomography (CT) scan OR
measurable disease in a lymphoid structure (spleen)

- Bone marrow involvement (greater than 20% of marrow cellularity)

- Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2

- See Disease Characteristics

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9.0 g/dL

- Bilirubin no greater than 2 times normal

- Aspartate aminotransferase (AST) no greater than 2 times normal

- Creatinine no greater than 2.0 mg/dL

- Creatinine clearance at least 50 mL/min

- No renal dysfunction that would impair tolerance or compliance with study therapy

- No cardiac dysfunction that would impair tolerance or compliance with study therapy

- No pulmonary dysfunction that would impair tolerance or compliance with study therapy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short
gut syndrome) that would impair tolerability of compliance with therapy

- No neurological or psychiatric dysfunction that would impair tolerability of or
compliance with study therapy

- At least 6 weeks since prior nitrosourea or mitomycin

- No more than 6 prior courses of fludarabine

- No concurrent corticosteroids as antiemetics

- At least 4 weeks since prior therapy for disease

- No more than 3 prior treatments for disease (not including steroids alone)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) defined as that dose level beneath the dose at which 2 or more of 6 patients experience dose limiting toxicity (DLT)

Outcome Time Frame:

Day 28

Safety Issue:

Principal Investigator

John Byrd

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01434

NCT ID:

NCT00058227

Start Date:

April 2003

Completion Date:

Related Keywords:

B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Contiguous Stage II Marginal Zone Lymphoma
Contiguous Stage II Small Lymphocytic Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Progressive Hairy Cell Leukemia, Initial Treatment
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Splenic Marginal Zone Lymphoma
Stage I Chronic Lymphocytic Leukemia
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Marginal Zone Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Untreated Hairy Cell Leukemia
Waldenström Macroglobulinemia
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Follicular
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell

Name	Location
Ohio State University Medical Center	Columbus, Ohio 43210

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Trial Information

Inclusion Criteria:

Type of Study:

Study Design:

Outcome Measure:

Outcome Time Frame:

Safety Issue:

Principal Investigator

Investigator Role:

Investigator Affiliation:

Authority:

Study ID:

NCT ID:

Start Date:

Completion Date:

Related Keywords:

Name

Location