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

June 3, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

37

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
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
Day 28

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

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

April 1, 2003

Primary Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

April 7, 2003

First Submitted That Met QC Criteria

April 8, 2003

First Posted (Estimate)

April 9, 2003

Study Record Updates

Last Update Posted (Estimate)

June 4, 2013

Last Update Submitted That Met QC Criteria

June 3, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01434
  • U01CA076576 (U.S. NIH Grant/Contract)
  • OSU 0211
  • OSU-02H0281
  • CDR0000287196
  • NCI-5745
  • OSU-0211

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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