Flavopiridol in Treating Patients With Relapsed or Refractory Multiple Myeloma

Refractory Multiple Myeloma Clinical Trial

Official title:

A Phase II Study of Flavopiridol in Patients With Relapsed and Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047203
• Other study ID #: NCI-2012-02496
• Secondary ID: MC018BN01CM17104
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2002
• Last updated: January 15, 2013
• Start date: September 2002

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage I Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• alvocidib
Given IV

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Ninety percent confidence intervals for the true success proportion will be calculated assuming a binomial distribution.	First 3 months of treatment	No
Secondary	Overall survival time	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 1 year	No
Secondary	Time to disease progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from registration to documentation of disease progression, assessed up to 1 year	No