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

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