A Phase I/II Clinical Trial of Lenalidomide in Combination With AT-101 for the Treatment of Relapsed B-cell Chronic Lymphocytic Leukemia (B-CLL)


Jacksonville, Fla.

Trial status:

Open for Enrollment

Why is this study being done?

This is an open-label, single institute Phase I/II non-randomized study. Patients with relapsed or refractory CLL (received at least one prior therapy for B-CLL) will be eligible for this study. Phase I: Patients will receive a fixed dose of AT-101 (40mg orally twice daily x 3 days) while the dose of lenalidomide will be escalated in subsequent patient cohorts. Starting dose of lenalidomide will be 5mg/day and the dose will increase by 5mg/day to a maximum of 20mg/day in 4 separate cohorts. Each patient cohort must have at least 3 patients. Dose limiting toxicity will be determined during the first combination (Lenalidomide + AT-101) cycle (cycle 2). Both drugs will be given on a 21-day schedule where lenalidomide will be given on day 1 through day 21 of all cycles and AT-101 will be given on days 1, 2 and 3 or cycles 2-12. This 21 day period will constitute a treatment cycle. Patients will receive a maximum of 12 cycles of treatment and during the first cycle, only single agent lenalidomide will be given. AT-101 will be added starting day 1 of cycle #2. Patients will be evaluated for response every two cycles and those patients who show some degree of response (defined as CR, PR, or SD) will continue treatment. Those patients who show disease progression at any time will be taken off the clinical protocol. Since the study will be investigating the maximum tolerated dose (MTD) of lenalidomide in combination with fixed dose of AT-101, the MTD will be established during the 2nd cycle of treatment instead of the first (this cycle will actually be the first cycle of the combination regimen). MTD will be determined during day 1 through day 21 of cycle 2. Once the MTD of the combination is established, Phase II section of the study will then be open to accrual. All patients in the phase I portion of the study must have completed at least 2 cycles of the combination therapy prior to opening the Phase II portion of the study for accrual. This will allow better characterization of the toxicity profile of the combination.

Who is eligible to participate?

Inclusion Criteria - Understand and voluntarily sign an informed consent form. - Age ≥ 18 years. - Able to adhere to the study visit schedule and other protocol requirements. - Diagnosis of B-CLL, confirmed by flow cytometric analysis and as per the criteria outlined by the IWCLL/Hallek December 2008. (Refer to Appendix III). - Any prior therapy for B-CLL must have been discontinued at least 28-days prior to treatment in this study. - Patients must have an absolute lymphocyte counts (ALC) of more than 5,000 cell/mm3. - During Phase I: All patients with relapsed disease will be eligible if they have received at least 1 prior standard CLL therapy* and no more than 4 prior therapies (one of which must be a purine analog and/or an alkylating agent). - During Phase II: All patients with relapsed disease will be eligible if they have received a minimum of 1 prior standard therapy* and a maximum of 2 prior treatments (one of which must be a purine analog and/or an alkylating agent) for B-CLL and have developed relapse disease. Note: patients with refractory CLL will not be eligible. * Standard Therapies are defined as those listed in the NCCN guidelines for treatment of CLL. - ECOG performance status of ≤ 2 at study entry (see Appendix I). - Laboratory test results within these ranges: - Absolute neutrophil count ≥ 1.5 x 109/L - Platelet count ≥ 30 x 109/L - Serum creatinine ≤ 1.5 x ULN. - Total bilirubin ≤ 1.5 mg/dL - AST (SGOT) and ALT (SGPT) ≤ 2 x ULN or ≤ 5 x ULN if hepatic disease is present. - Females of childbearing potential (FCBP) † must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and again within 24 hours before starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix VI: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix VII: Education and Counseling Guidance Document and Appendix VIII: lenalidomide information: - A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). - All study participants must be registered into the mandatory RevAssist ® program, and be willing and able to comply with the requirements of RevAssist® - Patients must require treatment for symptomatic B-Cell as defined by the IWCLL/Hallek, December 2008 criterion (see Appendix IV) or as determined clinically necessary by the treating physician. - Willing to provide blood samples for correlative research purposes (see Section 6.31 and Section 14.0). Exclusion Criteria - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. - Pregnant or lactating females. - Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. - Use of any other experimental drug or therapy within 28 days of baseline. - Known hypersensitivity to thalidomide or lenalidomide. - The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. - Patients who have not been treated with any prior therapy for B-CLL or those who have more than 4 prior therapies (for patients on phase 1 portion only) or 2 prior therapies for CLL (for patients on phase II part of the study). Also, patient who have refractory disease (defined as - progressive disease on last treatment, or less than 6 months of clinical response to the last treatment) will not be eligible. - Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for >3 years). - Patient with history of cardiac arrest within the past 6 months. - Patients with history of prior bowel resection, malabsorption syndrome, inflammatory bowel disease, prior bowel obstruction (partial or complete), Crohn disease, or any other disease significantly effecting the gastrointestinal tract. - Prior use of gossypol or AT-101 or prior history of hypersensitivity reaction to gossypol of AT-101

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