Flavopiridol in Treating Patients With Relapsed or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047203
First received: October 3, 2002
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase II trial to study the effectiveness of flavopiridol in treating patients who have relapsed or refractory multiple myeloma


Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: alvocidib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Flavopiridol in Patients With Relapsed and Refractory Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Confirmed response (CR, VGPR, or PR) defined as a patient who has achieved response and maintained it on two consecutive evaluations at least 4 weeks apart. [ Time Frame: First 3 months of treatment ] [ Designated as safety issue: No ]
    Ninety percent confidence intervals for the true success proportion will be calculated assuming a binomial distribution.


Secondary Outcome Measures:
  • Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 1 year ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Time to disease progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 1 year ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.


Enrollment: 35
Study Start Date: September 2002
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (flavopiridol)
Patients receive flavopiridol IV over 1 hour on days 1-3. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. After 12 months, patients achieving at least a partial response may continue treatment in the absence of disease progression or unacceptable toxicity.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the response rate in patients with relapsed or refractory multiple myeloma treated with flavopiridol.

II. Determine the disease-free survival and overall survival of patients treated with this drug.

III. Correlate disease response with t(11;14)(q13;q32) rearrangement, p16 methylation status, and BCRP expression in patients treated with this drug.

IV. Correlate disease response and drug treatment with cell cycle status and effects on apoptosis and apoptosis regulatory proteins in these patients.

OUTLINE: This is a multicenter study.

Patients receive flavopiridol IV over 1 hour on days 1-3. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. After 12 months, patients achieving at least a partial response may continue treatment in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of relapsed or refractory multiple myeloma (MM) requiring treatment

    • Durie-Salmon stage I or greater at diagnosis

      • Patients with non-secretory or oligo-secretory MM (defined as maximum urinary M-spike less than 200 mg/24 hours and a maximum serum M-spike less than 0.5 g/dL during entire disease course) must have at least 30% bone marrow plasma cells
      • Patients with secretory MM must have measurable disease defined as serum monoclonal protein of at least 1 g/dL or urinary M-spike of at least 200 mg/24 hours
  • Must have received at least 1, but no more than 5 prior therapy regimens

    • Patients who have had 4 or 5 regimens are allowed provided corticosteroids and/or thalidomide are part of the regimens
    • No more than 5 prior chemotherapy regimens (as long as 2 contained dexamethasone or thalidomide)
    • Prior autologous peripheral blood stem cell transplantation is considered 1 prior regimen
  • Performance status - ECOG 0-2
  • Performance status - ECOG 0-3 if secondary to neuropathy or acute bone event (e.g., vertebral compression or rib fracture)
  • Absolute neutrophil count at least 750/mm^3
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2.5 times ULN
  • AST no greater than 2.5 times ULN
  • Creatinine no greater than 3 mg/dL
  • No myocardial infarction within the past 6 months
  • Peripheral neuropathy secondary to prior drug therapy or myeloma-associated neuropathy allowed
  • No other uncontrolled serious medical condition
  • No uncontrolled infection
  • No other active malignancy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • See Disease Characteristics
  • No prior allogeneic stem cell transplantation
  • At least 10 days since prior thalidomide
  • No concurrent biologic therapy
  • See Disease Characteristics
  • At least 2 weeks since prior myelosuppressive chemotherapy
  • No other concurrent chemotherapy
  • See Disease Characteristics
  • No concurrent corticosteroids (including as antiemetics) except chronic corticosteroids for disorders other than myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)

    • Maximum dose allowed for prednisone is no more than 10 mg/day or hydrocortisone no more than 40 mg/day
  • At least 10 days since prior bortezomib or tipifarnib
  • Concurrent bisphosphonates allowed if on stable dose before study entry
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047203

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Angela Dispenzieri Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00047203     History of Changes
Other Study ID Numbers: NCI-2012-02496, MC018B, N01CM17104, CDR0000257567
Study First Received: October 3, 2002
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Alvocidib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014