Expired Study
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Columbus, Ohio 43210


Purpose:

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.


Study summary:

PRIMARY OBJECTIVES: I. Determine the disease-specific dose-limiting toxicity and maximum tolerated dose of flavopiridol in patients with relapsed or refractory lymphoma or multiple myeloma. II. Determine the complete and partial response rate in patients with selected non-Hodgkin's lymphoma (e.g., indolent B-cell, mantle cell, intermediate grade B-cell, and T/NK-cell), Hodgkin's lymphoma, or multiple myeloma treated with this drug. III. Determine the qualitative and quantitative toxic effects or this drug, in terms of organ specificity, time course, predictability, and reversibility in these patients. IV. Determine subsets of lymphoid/plasma cell malignancies that are suitable for larger phase II studies designed to further evaluate the efficacy and toxicity of this drug in these patients. SECONDARY OBJECTIVES: I. Determine the pharmacokinetics of this drug in these patients. II. Determine the effect of this drug on innate immunity (including T-, B-, and NK-cell subsets) and quantitative immunoglobulin levels in these patients. III. Determine whether acute infusion toxicity (e.g., fever, hypotension, tumor pain, and dyspnea) observed with other flavopiridol treatment schedules is related to a cytokine-release syndrome in these patients. IV. Determine whether this drug induces response (independent of p53 mutational status) in these patients. OUTLINE: This is a phase I, dose-escalation study followed by a multicenter, phase II, pilot study. Patients enrolled in the phase II portion of the study are stratified according to diagnosis. PHASE 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. NOTE: The phase II treatment dose and schedule for hairy cell leukemia patients will be adapted from that developed in previous phase II studies of flavopiridol for the treatment of chronic lymphocytic leukemia. After completion of study therapy, patients are followed every 3 months for 2 years.


Criteria:

Inclusion Criteria: - 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, 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 - Ineligible for potentially curative autologous stem cell transplantation - Stratum 4: T-cell and natural killer-cell NHL, including anaplastic large cell lymphoma and peripheral T-cell NHL - Primary cutaneous lymphoma or Sezary syndrome allowed provided criteria for measurable disease are met - Received ≥ 1 prior systemic therapy - Stratum 5: Hodgkin's lymphoma - Any of the following subtypes are allowed: - Nodular sclerosing - Mixed cellularity - Lymphocyte predominant - Lymphocyte depleted - Ineligible for potentially curative autologous stem cell transplantation - Stratum 6: Progressive stage I or stage II or IIIA multiple myeloma meeting ≥ 1 major and 1 minor criterion OR ≥ 3 minor criteria as follows: - Major criteria - Plasmacytoma on tissue biopsy - Bone marrow plasmacytosis ≥ 30% of marrow cellularity - Monoclonal paraprotein ≥ 3,500 mg/dL (IgG), or ≥ 2,000 mg/dL (IgA), OR monoclonal protein (Bence-Jones protein) ≥ 1,000 mg by 24-hour urine collection - Minor criteria - Bone marrow plasmacytosis 10-29% of marrow cellularity - Monoclonal paraprotein < 3,500 mg/dL (IgG) or < 2,000 mg/dL (IgA) - Lytic bone lesions by x-ray or CT scan - Decrease in normal IgM (< 50 mg/dL), IgA (< 100 mg/dL), or IgG (< 600 mg/dL) - Relapsed or refractory disease - Measurable disease, defined by 1 of the following: - At least 1 node > 2 cm by CT scan - Measurable disease in a lymphoid structure (i.e., spleen) by CT scan - Bone marrow involvement (> 20% of marrow cellularity) - Patients with multiple myeloma must have detectable serum or urinary paraprotein - Patients with only cutaneous or subcutaneous disease (i.e., no measurable lymph node or bone marrow disease) are eligible if the extent of rash or skin involvement OR the size of the nodules are measurable - Must have received ≥ 1 prior therapy - Steroids alone are not considered prior therapy for patients with NHL or Hodgkin's lymphoma - High-dose dexamethasone is considered 1 prior therapy for patients with multiple myeloma - No standard effective therapy exists - No HIV-associated lymphoma - No nonsecretory multiple myeloma - Performance status - ECOG 0-2 - No concurrent hormonal therapy except steroids for new adrenal failure or hormones administered for non-disease-related conditions (e.g., insulin for diabetes) - Hemoglobin ≥ 9.0 g/dL* - Absolute neutrophil count ≥ 1,500/mm^3* - Platelet count ≥ 50,000/mm^3* - AST ≤ 3 times upper limit of normal (ULN) - Bilirubin ≤ 2 times ULN - No major renal dysfunction that would preclude study compliance or participation - Phase I: - Creatinine ≤ 1.5 mg/dL - Creatinine clearance ≥ 70 mL/min - Phase II: - Creatinine ≤ 2.0 mg/dL - Creatinine clearance ≥ 50 mL/min - No cardiac or vascular dysfunction that would preclude central venous access, vigorous hydration, or hemodialysis - No other major cardiac dysfunction that would preclude study compliance or participation - No major pulmonary dysfunction that would preclude study compliance or participation - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No chronic gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) that would preclude study compliance or participation - No other major organ system (including neurological or psychiatric) dysfunction that would preclude study compliance or participation - Prior radiotherapy, including radioimmunotherapy, allowed - No concurrent radiotherapy - Prior idiotype vaccination or stem cell transplantation allowed - More than 6 weeks since prior mitomycin or nitrosoureas - No other concurrent chemotherapy - More than 4 weeks since other prior therapy - Prior systemic steroids allowed


Study is Available At:


Original ID:

NCI-2011-01346


NCT ID:

NCT00112723


Secondary ID:

NCI-2011-01346


Study Acronym:


Brief Title:

Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma


Official Title:

A Phase I/II Study of Flavopiridol Administered as a 30-Minute Bolus Followed by a 4-Hour Infusion in Lymphomas and Multiple Myeloma


Overall Status:

Active, not recruiting


Study Phase:

Phase 1/Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, In


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

180


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Jeffrey Jones
Principal Investigator
Ohio State University

Study Dates

Start Date:December 2005
Primary Completion Date:February 2011
Primary Completion Type:Actual
Verification Date:December 2013
Last Changed Date:December 6, 2013
First Received Date:June 2, 2005

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Pharmacodynamic effects of flavopiridol on normal peripheral blood mononuclear cells (PBMCs).
Time Frame:Day 1
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Induced response in patients independent of p53 mutational status
Time Frame:Up to 2 years
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Acute infusion toxicity (e.g., fever, hypotension, tumor pain, and dyspnea)
Time Frame:Up to 30 days after completion of study treatment
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Pharmacokinetics of flavopiridol
Time Frame:Days 1 and 22
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Lymphoid/plasma cell malignancies
Time Frame:Up to 2 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility as measured by CTCAE version 4.0
Time Frame:Up to 30 days after completion of study treatment
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Complete and partial response rate (Phase II)
Time Frame:Up to 2 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Disease-specific dose-limiting toxicity and maximum tolerated dose of flavopiridol graded according to the CTCAE version 4.0 (Phase I)
Time Frame:28 days
Safety Issues:True
Description: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 t

Study Interventions

Intervention Type:Drug
Name:alvocidib
Description:Given IV
Arm Name:Treatment (alvocidib)
Other Name:FLAVO

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (alvocidib)
Description:PHASE 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

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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