Know Cancer

or
forgot password

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


Phase 1
18 Years
N/A
Not Enrolling
Both
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

Thank you

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:

No

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 CenterColumbus, Ohio  43210