Study Stopped
Administratively Complete
Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
A Phase I/II Study of Flavopiridol Administered as a 30-Minute Bolus Followed by a 4-Hour Infusion in Lymphomas and Multiple Myeloma
10 other identifiers
interventional
46
1 country
1
Brief Summary
This phase I/II trial is studying the side effects and best dose of flavopiridol and to see how well it works in treating patients with lymphoma or multiple myeloma. Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2005
Longer than P75 for phase_1
1 active site
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
First Submitted
Initial submission to the registry
June 2, 2005
CompletedFirst Posted
Study publicly available on registry
June 3, 2005
CompletedStudy Start
First participant enrolled
December 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2015
CompletedResults Posted
Study results publicly available
August 8, 2016
CompletedAugust 8, 2016
June 1, 2016
5.2 years
June 2, 2005
March 23, 2015
June 27, 2016
Conditions
Outcome Measures
Primary Outcomes (5)
Disease-specific Dose-limiting Toxicity and Maximum Tolerated Dose of Flavopiridol Graded According to the CTCAE (Common Toxicity Criteria for Adverse Effects) Version 4.0 (Phase I)
Dose limiting toxicity (DLT) for an individual disease group is defined as 1) any grade 3-4 non-hematologic toxicity (except leukopenia or neutropenia) that does not resolve or decrease to grade 1-2 within 2 weeks, or 2) any grade 4 hematologic toxicity that causes more than a 1 week delay in administration of therapy.
28 days
Maximum Tolerated Dose (MTD)
The maximum tolerated dose (MTD) is defined as that dose level beneath the dose at which 2 or more of 6 patients experience DLT.
28 days
Complete and Partial Response Rate (Phase II)
Patients were assessed for clinical response after two , four and six cycle with laboratory studies, physical exam, and CT scans. Response was evaluated using the modified NCI-sponsored Working Group Lymphoma Response Criteria.
Up to 2 years
Qualitative and Quantitative Toxicities in Regard to Organ Specificity
The NCI Common Toxicity Criteria for Adverse Events (version 3.0) were used to define and grade toxicity for patients.
Up to 30 days after completion of study treatment
Lymphoid/Plasma Cell Malignancies
Identify subsets, based on levels of response (PR and SD), of lymphoid / plasma cell malignancies that are suitable for larger phase II studies designed to further evaluate the efficacy and toxicity of flavopiridol.
Up to 2 years
Secondary Outcomes (5)
Pharmacokinetics (Area Under the Curve; AUC) of Flavopiridol
0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 22 of Cycle 1
Number of Patients Reporting Acute Infusion Toxicity (e.g., Fever, Hypotension, Tumor Pain, and Dyspnea)
Up to 30 days after completion of study treatment
Induced Response in Patients Independent of p53 Mutational Status
Up to 2 years
Pharmacodynamic Effects of Flavopiridol on Normal Peripheral Blood Mononuclear Cells (PBMCs).
Day 1
Pharmacokinetics (Cmax) of Flavopiridol
0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Days 1 and 22 of Cycle 1
Study Arms (1)
Treatment (alvocidib)
EXPERIMENTALPHASE I: Patients receive flavopiridol IV over 4½ hours on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PHASE II: Patients receive flavopiridol\* as in phase I at the MTD determined in phase I.
Interventions
Eligibility Criteria
You may qualify if:
- Diagnosis of 1 of the following hematologic malignancies:
- Hodgkin's lymphoma
- Non-Hodgkin's lymphoma (NHL)
- Multiple myeloma
- Patients in the phase II portion of the study are enrolled in 1 of the following strata according to diagnosis\*
- Stratum 1: Indolent B-cell NHL (non-Hodgkin's lymphoma), follicle center B-cell NHL (grade 1, 2, or 3), marginal zone lymphoma, Waldenstrom's macroglobulinemia, or small lymphocytic lymphoma (without blood lymphocytosis at any point in the disease process)
- Must have progressive lymphadenopathy, worsening cytopenias, or progressive symptoms attributed to lymphoma
- Must require therapy, as determined by progressive anemia, thrombocytopenia, symptoms (e.g., fever, night sweats, weight loss, or fatigue), or progressive lymphadenopathy that causes discomfort
- Received ≥ 2 prior therapies, including rituximab
- Stratum 1a: Hairy cell leukemia
- Must require therapy, as determined by progressive cytopenias or symptoms (fever, night sweats, weight loss, or fatigue)
- Must have received ≥ 2 therapies
- Stratum 2: Mantle cell lymphoma, as determined by the presence of cyclin D1 staining OR t(11;14)
- Stratum 3: Intermediate grade B-cell NHL, including diffuse large B-cell NHL and T-cell rich B-cell NHL
- Diffuse large B-cell NHL arising from an indolent NHL (i.e., transformed lymphoma) allowed
- +63 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Related Publications (1)
Hofmeister CC, Poi M, Bowers MA, Zhao W, Phelps MA, Benson DM, Kraut EH, Farag S, Efebera YA, Sexton J, Lin TS, Grever M, Byrd JC. A phase I trial of flavopiridol in relapsed multiple myeloma. Cancer Chemother Pharmacol. 2014 Feb;73(2):249-57. doi: 10.1007/s00280-013-2347-y. Epub 2013 Nov 16.
PMID: 24241210DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jeffrey Jones, MD
- Organization
- The Ohio State University Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Jeffrey Jones
Ohio State University
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
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
June 2, 2005
First Posted
June 3, 2005
Study Start
December 1, 2005
Primary Completion
February 1, 2011
Study Completion
November 1, 2015
Last Updated
August 8, 2016
Results First Posted
August 8, 2016
Record last verified: 2016-06