Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for Adult Lymphocyte Depletion Hodgkin Lymphoma
Eligibility 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 (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 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 (Eastern Cooperative Oncology Group) 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 (aspartate aminotransferase) ≤ 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
Sites / Locations
- Ohio State University Medical Center
Arms of the Study
Arm 1
Experimental
Treatment (alvocidib)
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.