Flavopiridol in Treating Patients With Previously Untreated or Relapsed Mantle Cell Lymphoma

NCIC Clinical Trials Group

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: alvocidib

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00005074

I127

NCI-100 (Other Identifier)

CAN-NCIC-IND127 (Other Identifier)

CDR0000067679 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of flavopiridol in treating patients who have previously untreated or relapsed mantle cell lymphoma.

Full description

OBJECTIVES:

• Assess the efficacy of flavopiridol in terms of response rate in patients with previously untreated or relapsed mantle cell lymphoma.
• Assess the toxicity of this regimen in this patient population.
• Determine the time to progression and, if responses are observed, response duration in these patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive flavopiridol IV over 1 hour daily for 3 days. Treatment continues every 3 weeks in the absence of unacceptable toxicity or disease progression. Patients with a complete response (CR) receive 2 additional courses after documented CR. Patients with a partial response receive 2 additional courses after documented maximal tumor shrinkage. Patients with stable disease receive a maximum of 4 courses.

Patients are followed at 4 weeks and then every 3 months until relapse or death.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 18-24 months.

Enrollment: 33 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed mantle cell lymphoma (at initial diagnosis) nonrefractory to prior therapy or with no prior therapy

  • No documented disease progression while receiving prior chemotherapy

• CD20 and CD5 positive

• Presence of clinically and/or radiologically documented disease

• At least 1 site of disease must be bidimensionally measurable

  • Bone lesions not considered bidimensionally measurable

  • Minimum indicator lesions must be:

    • Lymph nodes at least 1.5 cm x 1.5 cm by physical exam or spiral CT scan OR
    • Other nonnodal lesions at least 1 cm x 1 cm by MRI, CT scan, or physical exam

• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 75,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit or normal (ULN)
• AST no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No clinically significant cardiac symptomatology
• If history of cardiac disease, cardiac ejection fraction greater than 50%

Pulmonary:

• No clinically significant pulmonary symptomatology

• If history of symptomatic pulmonary disease:

  • FEV1, FVC, and TLC greater than 60% predicted
  • DLCO greater than 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be accessible for treatment and follow-up (i.e., no geographical limitations)
• No uncontrolled bacterial, fungal, or viral infection
• No other serious concurrent disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior radioactive monoclonal antibody therapy
• Prior rituximab allowed

Chemotherapy:

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens allowed
• Same chemotherapy combination given for first line and second line therapy considered 2 regimens
• At least 6 weeks since prior chemotherapy
• No prior high-dose chemotherapy and stem cell transplantation
• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No prior radiotherapy to greater than 25% of functioning bone marrow
• At least 4 weeks since prior radiotherapy (except low-dose, non-myelosuppressive radiotherapy) and recovered
• No concurrent radiotherapy to sole site of measurable disease

Surgery:

• At least 2 weeks since prior major surgery

Other:

• No other concurrent investigational anticancer agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)