Lenalidomide in Treating Patients With High Risk Acute Myeloid Leukemia in Remission

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well lenalidomide works in treating patients with acute myeloid leukemia that have had a decrease in or disappearance of signs and symptoms of cancer, although cancer still may be in the body and may be likely to come back or spread. Biological therapies, such as lenalidomide, use substances made from living organisms that may kill cancer cells by blocking blood flow to the cancer and by stimulating white blood cells to kill the cancer cells.

Detailed Description
-----------------
PRIMARY OBJECTIVE: I. To assess relapse-free survival (RFS) of patients with acute myeloid leukemia (AML) treated with lenalidomide maintenance therapy after achieving remission. SECONDARY OBJECTIVES: I. To assess overall survival (OS) of patients with AML treated with lenalidomide maintenance. II. To assess event-free survival (EFS) of patients with AML treated with lenalidomide maintenance. III. To assess the duration of remission (CRd) of patients with AML treated with lenalidomide maintenance. IV. To assess toxicity and safety of lenalidomide maintenance in patients with AML. V. To assess the effects of lenalidomide maintenance on natural killer (NK) cell modulation and dynamics of minimal residual disease and their relationship to outcomes. OUTLINE: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.

Official Title
-----------------
Phase II Study of Lenalidomide Maintenance in Patients With High Risk AML in Remission

Conditions
-----------------
Alkylating Agent-Related Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Other: Laboratory Biomarker Analysis
* Drug: Lenalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18 to 55 years with high risk AML who have achieved their FIRST complete remission (CR) or complete remission with incomplete recovery (CRi) within 12 months of enrollment and are not immediately candidates for allogeneic stem cell transplant; patients above age 55 who are not eligible for other protocols may be considered for enrollment on a case by case basis after discussion with the principal investigator (PI) Patients in their FIRST CR or CRi may be eligible for enrollment only if they have a high risk feature, including, but not limited to: adverse karyotype, fms-related tyrosine kinase 3 (FLT3) mutation, history of antecedent hematologic disorder (AHD), presence of dysplasia in the bone marrow, therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, or presence of persistent minimal residual disease (detected by cytogenetics, molecular markers, or flow cytometry) at any point after initial induction cycle; patients aged >= 18 years with AML who have achieved a SECOND CR or CRi within 12 months of enrollment and are not immediately candidates for allogeneic stem cell transplant are also eligible Patients should have received induction chemotherapy for AML and at least 1 consolidation Patients with history of extramedullary AML, except for central nervous system (CNS) involvement that is currently controlled, will not be eligible for enrollment Eastern Cooperative Oncology Group (ECOG) performance status of < or = 3 Serum total bilirubin < or = to 1.5 X the upper limit of normal (ULN) Serum creatinine < or = to 2.5 x ULN Absolute neutrophil count (ANC) > 0.5 x 10^9/L Platelet count > or = 30 x 10^9/L For females of childbearing age, they may participate it they: a. have a negative serum or urine pregnancy test within 10 to 14 days of enrolling (a second pregnancy test will be performed within 24 hours (hrs) of starting therapy and both negative pregnancy tests will be required for starting therapy); b. agree to either abstinence or 2 effective contraceptive methods throughout the treatment period and up to 28 days after discontinuing treatment For male patients with a female partner of childbearing age, they may participate if they agree to either abstinence or 2 effective contraceptive methods throughout the treatment period and up to 28 days after discontinuing treatment All study participants be willing and able to comply with the requirements of the Risk Evaluation and Mitigation Strategies (REMS) program Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program Ability to understand and sign informed consent Exclusion Criteria: Diagnosis of acute promyelocytic leukemia (APL), AML - M3 by French American British (FAB) classification based on morphology, immunophenotype, molecular, or cytogenetics studies Diagnosis of AML associated with the following karyotypes: inversion (inv)(16), t(16;16), t(8;21), t(15;17), or t(9;22) Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Previous treatment with lenalidomide for AML Patients with documented hypersensitivity to any components of the study program Females who are pregnant Patients with active CNS disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lenalidomide)<br>Patients receive lenalidomide PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Lenalidomide<br>* Given PO<br>* Other names: Revlimid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free Survival (RFS) | Time from date of treatment start until the date of first objective documentation of disease-relapse. | Up to 7 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. | Up to 7 Years | 
| Event-free Survival (EFS) | Time from date of treatment start until the date of first objective documentation of disease-relapse, death or discontinuation due to adverse events. | Up to 7 Years | 
| Complete Response (CR) Duration | Complete Response is defined as disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count >/= 1.0 x 10^9/L and platelet count>/= 100 x 10^9, and bone marrow differential showing </=5%blasts. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. | Up to 7 years |