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)
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- Recurrent Chronic Lymphocytic Leukemia
- Sponsor
- Mayo Clinic
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
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 B-cell chronic lymphocytic leukemia (B-CLL) that has returned after a period of improvement (relapsed). Biological therapies, such as lenalidomide, may stimulate the immune system to attack cancer cells. R-(-)-gossypol acetic acid may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and causing the cells to die. Giving lenalidomide with R-(-)-gossypol acetic acid may be an effective treatment for relapsed or refractory B-CLL. - Funding Source - FDA OOPD
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with AT-101 (R-(-)-gossypol acetic acid). (Phase I) II. To assess the overall response rate of lenalidomide in combination with AT-101. (Phase II) SECONDARY OBJECTIVES: I. To assess the overall response rates of lenalidomide in combination with AT-101 at 6 months and 12 months. II. To evaluate time to progression (TTP) for the combination of lenalidomide + AT-101. III. To evaluate the safety of this combination in patients with relapsed B-CLL. TERTIARY OBJECTIVES: I. 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 28 days for up to 11 courses (49-56 days for course 12 or last course of treatment) 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 months for up to 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Understand and voluntarily sign an informed consent form
- •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 International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/Hallek December 2008
- •Any prior therapy for B-CLL must have been discontinued \>= 28-days prior to registration
- •Patients must have absolute lymphocyte counts (ALC) of more than 5,000 cell/mm\^3
- •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 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at registration
- •Absolute neutrophil count \>= 1500/mm\^3
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 =\< 28 days prior to registration
- •Known hypersensitivity to thalidomide or lenalidomide
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
- •Patients with of history of any other cancer (except nonmelanoma 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 affecting the gastrointestinal tract
- •Prior use of gossypol or AT-101
Arms & Interventions
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 28 days for up to 11 courses (49-56 days for course 12 or last course of treatment) in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
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 28 days for up to 11 courses (49-56 days for course 12 or last course of treatment) in the absence of disease progression or unacceptable toxicity.
Intervention: R-(-)-Gossypol Acetic Acid
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 28 days for up to 11 courses (49-56 days for course 12 or last course of treatment) in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: Up to day 28 of course 2
Maximum tolerated dose of lenalidomide when given in combination with AT-101, defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)
Overall Response Rate (Complete Response [CR], CR With Incomplete Marrow Recovery, Clinical CR, Nodular Partial Response [PR], and PR) (Phase II)
Time Frame: Up to 2 years
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Secondary Outcomes
- Incidence of Toxicity, Defined as Adverse Events Classified as Possibly, Probably, or Definitely Related to Study Treatment, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies or Ordinal Common Toxicity Criteria (Phase I)(Up to 2 years)
- Incidence of Adverse Events, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies (Phase I)(Up to 2 years)
- Overall Response Rate (Phase II)(Up to 12 months)
- Time to Progression (Phase II)(The time from registration to the earliest date of documentation of disease progression, assessed up to 2 years)
- Incidence of Adverse Events, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies (Phase II)(Up to 30 days after the last day of study treatment)