Lenalidomide and AT-101 in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
This phase I/II trial studies the side effects and best dose of lenalidomide when given together with R-(-)-gossypol acetic acid and to see how well they work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as R-(-)-gossypol acetic acid, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage IV Chronic Lymphocytic Leukemia
Drug: R-(-)-gossypol acetic acid
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Maximum tolerated dose of lenalidomide when given in combination with AT-101 [ Time Frame: Days 1-21 of course 2 ] [ Designated as safety issue: Yes ]Defined as the dose one level below the dose at which >= 2 of 3 patients or >= 2 of 6 patients experience dose-limiting toxicity during course 2.
- Overall response rate (CR and PR) of including lenalidomide in combination with AT-101 [ Time Frame: At 6 and 12 months ] [ Designated as safety issue: No ]
- Frequency of subjects experiencing a specific adverse event [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Tabulated by body system, MedDRA term, and treatment cohort and summarized by worst NCI Common Toxicity Criteria (CTC) grade.
- Time to progression for the combination of lenalidomide and AT-101 [ Time Frame: Until the time of disease progression, assessed up to 12 months ] [ Designated as safety issue: No ]
- Effect of lenalidomide on the immune effector arm (T and NK cells) in peripheral blood [ Time Frame: Days 0, 1, 8, and 15 of course 1 and day 1 of course 2 ] [ Designated as safety issue: No ]
- Changes in the immune cellular micro environment in bone marrow aspirate [ Time Frame: At baseline and day 1 of course 2 ] [ Designated as safety issue: No ]
- Effect of specific molecular targets (including MCI-1, Akt, Erk1/2, Bcl-2, Bcl-xl, Puma, Noxa, and XIP) by Western blot analysis of peripheral blood [ Time Frame: At baseline, days 1, 8, and 15 of courses 1-2, and day 1 of course 3 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (lenalidomide in combination with AT-101)
Patients receive lenalidomide PO QD on days 1-21. Beginning in course 2, patients also receive AT-101 PO BID on days 1-3. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: R-(-)-gossypol acetic acid
Other Name: AT-101
I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with AT-101 (R-(-)-gossypol acetic acid).
II. To evaluate overall response rate including (complete response [CR] + partial response [PR]) of lenalidomide in combination with AT-101 at 6 and then at 12 months.
I. To evaluate the safety of this combination in patients with relapsed or refractory B-CLL.
II. Time to progression (TTP) for the combination of lenalidomide + AT-101. III. To conduct correlative studies for further understanding of the mechanism of antitumor activity of lenalidomide and lenalidomide + AT-101.
OUTLINE: This is a phase I dose-escalation study of lenalidomide followed by a phase II study.
Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Beginning in course 3, patients also receive AT-101 PO twice daily (BID) on days 1-3. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 3-4 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01003769
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Asher A. Chanan-Khan firstname.lastname@example.org|
|Principal Investigator: Asher A. Chanan-Khan|
|United States, New York|
|Roswell Park Cancer Institute||Terminated|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Asher Chanan-Khan||Mayo Clinic|