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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00058227
First Posted: April 9, 2003
Last Update Posted: June 4, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase I trial studies the side effects, best way to give, and the best dose of alvocidib when given together with fludarabine phosphate and rituximab in treating patients with previously untreated or relapsed lymphoproliferative disorders or mantle cell lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy such as alvocidib and fludarabine use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

Condition Intervention Phase
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 Drug: alvocidib Drug: fludarabine phosphate Biological: rituximab Other: pharmacological study Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Flavopiridol, Fludarabine and Rituximab in Indolent B-cell Lymphoproliferative Disorders and Mantle Cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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) [ Time Frame: Day 28 ]
  • DLT defined as any grade 3-4 non-hematologic toxicity that does not resolve or decrease to grade 1-2 within 2 weeks, or any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy [ Time Frame: Day 28 ]

Secondary Outcome Measures:
  • Toxicity as determined by National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 2.0 criteria [ Time Frame: Up to 6 years ]
  • Pharmacokinetic data [ Time Frame: Up to 6 years ]
  • Pharmacodynamic data [ Time Frame: Up to 6 years ]

Enrollment: 37
Study Start Date: April 2003
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (alvocidib, fludarabine phosphate, rituximab)
Patients receive fludarabine phosphate 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.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00058227


Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: John Byrd Ohio State University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058227     History of Changes
Other Study ID Numbers: NCI-2012-01434
OSU 0211
OSU-02H0281
CDR0000287196
NCI-5745
OSU-0211
U01CA076576 ( U.S. NIH Grant/Contract )
First Submitted: April 7, 2003
First Posted: April 9, 2003
Last Update Posted: June 4, 2013
Last Verified: June 2013

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma
Leukemia
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Leukemia, Hairy Cell
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Fludarabine
Fludarabine phosphate
Alvocidib
Rituximab