Lenalidomide After Allo-Hematopoietic Cell Transplant (HCT) in Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS) Subjects With Minimal Residual Disease

A Phase I Clinical Trial to Evaluate the Maximally Tolerated Dose (MTD), Dose Limiting Toxicities (DLTs) and Safety Profiles of Increasing Doses of Lenalidomide After Allo-HCT in AML and MDS Subjects With Minimal Residual Disease (MRD) Detected by the CD34+ Mixed Chimerism Analysis (UF-BMT-MRD-101)

The purpose of this study is to determine the maximum tolerated dose, dose limiting side effects, and the safety of increasing doses of lenalidomide in patients with AML and MDS who have a small amount of detectable disease after allogeneic stem cell transplant.

All subjects entering the screening phase will receive a unique subject number. This number will be used to identify the subject throughout the study. Additional test to include: physical examinations, blood tests, and if applicable pregnancy test will be performed as part of participation in this research study.

Lenalidomide will be administered for a total of 42 days. The starting dose will be 2.5 mg given orally every other day on days 1-21 of a 28-day cycle for 2 cycles. Dose escalations and de-escalations will be made until the maximum tolerated dose is reached.

The dose levels of lenalidomide will be as follows:

Dose Level 1: 2.5 mg

Dose Level 2: 2.5 mg

Dose Level 3: 5 mg

Dose Level 4: 7.5 mg

Doses should be taken at approximately the same time each day.

Subjects must be instructed to swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules.

Each subject will keep an accurate record of lenalidomide dosing on the Subject Dosing Diary. This diary will be kept in the research record as source documentation of lenalidomide dosing. Study personnel will review the dosing instructions with each subject at each study visit. Subjects will be asked to bring any unused drug and empty drug containers to the study site at the next visit for reconciliation with the Subject Dosing Diary.

Inclusion Criteria:

1. Subjects must be at least 18 years of age;

2. Subjects must be post-allogeneic transplant from any donor source;

3. Subjects must have either:

   1. High risk CD34+ AML (de novo or secondary, and any WHO 2008 classification excluding acute promyelocytic leukemia). High risk AML is defined as (a) disease status beyond complete remission (CR) #1 at transplant or (b) treatment related AML or (c) presence of adverse cytogenetics including inv(3); t(3;3); t(6;9); t(v;11); -5 or del(5q); -7; abnl(17p) or complex karyotype; or
   2. High risk CD34+ MDS (WHO 2008 classification). High risk is defined as (a) blast count ≥5% at the time of transplant or (b) treatment related MD or (c) presence of adverse cytogenetics including -7/del7q or complex karyotype;

4. For AML subjects, they must have a documented CR within 45 days prior to allo-HCT;

5. For MDS subjects, they must have < 20% myeloblasts in the bone marrow within 45 days prior to allo-HCT;

6. Subject Karnofsky performance status must be ≥ 70;

7. Subjects must be platelet transfusion independent (Platelet transfusion independence is defined as 7 days or greater without a platelet transfusion);

8. Neutrophil count ≥ 1.0 thou/mm3 and platelet count ≥ 30 thou/mm3;

9. Subjects must have total bilirubin ≤ 2 mg/dL;

10. Subjects must have serum AST and ALT levels ≤ 2.5 times upper limit of normal;

11. Subjects must have serum creatinine < 2.5 times upper limit of normal and a calculated creatinine clearance > 30 ml/min by Cockcroft-Gault formula (see Appendix I: Cockcroft-Gault Creatinine Clearance Calculation);

12. All study participants who will receive lenalidomide based on the CD34+ chimerism testing must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program;

13. Females of child-bearing potential (i.e., women who are premenopausal or not surgically sterile) may participate, provided they meet the following conditions:

    a) Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program; and

14. Written, voluntary informed consent, willingness, and ability to comply with all study procedures.

Exclusion Criteria:

1. CD34- AML or MDS;
2. Inability to give informed consent;
3. Uncontrolled active infection(s) requiring intravenous antibiotics;
4. Known or suspected hypersensitivity to lenalidomide;
5. Grade II-IV acute GVHD or extensive GVHD;
6. Not able to swallow the lenalidomide capsule as a whole;
7. Female subjects who are pregnant or nursing.