Multiple Myeloma Clinical Trial
R-(-)-Gossypol Acetic Acid With Lenalidomide and Dexamethasone in Treating Patients With Relapsed Symptomatic Multiple Myeloma
This phase I trial studies the side effects and best dose of R-(-)-gossypol acetic acid when given together with lenalidomide and dexamethasone and to see how well it works in treating patients with multiple myeloma, also known as plasma cell myeloma, that has come back after a period of improvement or has gotten worse after treatment. R-(-)-gossypol acetic acid may stop the growth of cancer cells by recognizing certain proteins and stimulating programmed cell death. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving R-(-)-gossypol acetic acid with lenalidomide and dexamethasone may work better in treating patients with multiple myeloma.
I. To determine the maximum tolerated dose of R-(-)-gossypol acetic acid (AT-101) that can be combined with lenalidomide and dexamethasone in patients with relapsed symptomatic multiple myeloma (MM). (Phase I) II. To determine the overall response rate (partial response or better) of AT-101 when used in combination with lenalidomide and dexamethasone in patients with relapsed symptomatic MM. (Phase II)
I. To determine the progression free survival and overall survival among patients with relapsed symptomatic MM following treatment with AT-101 in combination with lenalidomide and dexamethasone.
II. To determine the toxicities associated with AT-101 in combination with lenalidomide and dexamethasone in patients with relapsed symptomatic MM.
I. Determine in vivo the anti-myeloma effect of AT-101 alone by assessing extent of decrease in M-protein (serum and/or urine) after 1 cycle of AT-101 alone.
II. Determine the pharmacodynamics effect of AT-101 in combination with lenalidomide and dexamethasone treatment on primary myeloma cell in vivo.
III. Explore potential mechanism of resistance to AT-101 in combination with lenalidomide and dexamethasone therapy and the role of B-cell CLL/lymphoma 2 (Bcl-2).
OUTLINE: This is a phase I dose-escalation study of R-(-)-gossypol acetic acid followed by a phase II study.
Patients receive R-(-)-gossypol acetic acid orally (PO) once a day (QD) on days 1-21. Beginning in course 2, patients also receive lenalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, and 15. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 3 years.
Calculated creatinine clearance (using Cockcroft-Gault equation) >= 60 mL/min
Absolute neutrophil count (ANC) >= 1000/mm^3
Platelet count >= 75000/mm^3
Hemoglobin >= 8.0 g/dL
Patient must have relapsed and symptomatic multiple myeloma
Measurable disease of multiple myeloma as defined by at least ONE of the following:
Serum monoclonal protein >= 1.0 g/dL
> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Patients must have received at least 1 prior regimen
Provide informed written consent
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Willing to provide bone marrow and blood samples for correlative research purposes
Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
Patients who have received > 3 prior treatment regimens for multiple myeloma
Other malignancy requiring active therapy; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
Any of the following:
Men or women of childbearing potential who are unwilling to employ adequate contraception
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; Note: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
Prior severe skin reaction (toxic epidermal necrosis) with immunomodulating agents
Major surgery =< 14 days before study registration
Concurrent medical problems that preclude use of deep vein thrombosis (DVT) prophylaxis with lenalidomide treatment
Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction =< 6 months prior to registration
Known human immunodeficiency virus (HIV) positive
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
Known allergy to any of the study medications, their analogues or excipients in the various formulations
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There is 1 Location for this study
Jacksonville Florida, 32224, United States
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