NCT00058227

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2003

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

April 7, 2003

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 9, 2003

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2009

Completed
Last Updated

June 4, 2013

Status Verified

June 1, 2013

Enrollment Period

5.8 years

First QC Date

April 7, 2003

Last Update Submit

June 3, 2013

Conditions

B-cell Chronic Lymphocytic LeukemiaContiguous Stage II Grade 1 Follicular LymphomaContiguous Stage II Grade 2 Follicular LymphomaContiguous Stage II Mantle Cell LymphomaContiguous Stage II Marginal Zone LymphomaContiguous Stage II Small Lymphocytic LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaNoncontiguous Stage II Grade 1 Follicular LymphomaNoncontiguous Stage II Grade 2 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaNoncontiguous Stage II Small Lymphocytic LymphomaProgressive Hairy Cell Leukemia, Initial TreatmentRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Hairy Cell LeukemiaSplenic Marginal Zone LymphomaStage I Chronic Lymphocytic LeukemiaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Small Lymphocytic LymphomaStage II Chronic Lymphocytic LeukemiaStage III Chronic Lymphocytic LeukemiaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Small Lymphocytic LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaUntreated Hairy Cell LeukemiaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

  • 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)

    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

    Day 28

Secondary Outcomes (3)

  • Toxicity as determined by National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 2.0 criteria

    Up to 6 years

  • Pharmacokinetic data

    Up to 6 years

  • Pharmacodynamic data

    Up to 6 years

Study Arms (1)

Treatment (alvocidib, fludarabine phosphate, rituximab)

EXPERIMENTAL

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: alvocidibDrug: fludarabine phosphateBiological: rituximabOther: pharmacological study

Interventions

alvocidibDRUG

Given IV

Also known as: FLAVO, flavopiridol, HMR 1275, L-868275
Treatment (alvocidib, fludarabine phosphate, rituximab)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (alvocidib, fludarabine phosphate, rituximab)
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (alvocidib, fludarabine phosphate, rituximab)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (alvocidib, fludarabine phosphate, rituximab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Hairy CellWaldenstrom Macroglobulinemia

Interventions

alvocidibfludarabine phosphateRituximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • John Byrd

    Ohio State University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 7, 2003

First Posted

April 9, 2003

Study Start

April 1, 2003

Primary Completion

February 1, 2009

Last Updated

June 4, 2013

Record last verified: 2013-06

Locations

US(1)