Protocol Summary

Protocol No.: OCR13968

Sponsor Protocol No.: RV-CL-AML-PI-002987; UF-BMT-MRD-101

Study Title
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

Principal Investigator(s)
Norkin, Maxim

Objective
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.

Description
The CD34+ donor chimerism will be performed on days +60 and +90 (+/-7 days ) post-transplant until the CD34+ donor chimerism drops to ≤ 90%. If the CD34+ donor chimerism continues to be > 90% by day +90 post-transplant the patient will be removed from the study.

Treatment with lenalidomide will start within 5 days after the detection of the CD34+ donor chimerism ≤ 90% and be continued for 21 days in a 28 day cycle x 2 cycles or until terminating events occurs, whichever occurs first. In subjects receiving lenalidomide, the CD34+ donor chimerism will be performed at Days +60 and 120 (+/- 7days) of lenalidomide therapy.

Phase: Phase I

Age Group: Adult

Scope: Local

Treatment
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

Detailed Eligibility
Inclusion Criteria:
1. Subjects must be at least 18 years of age
2. Subjects must be at least 60 days post-allogeneic transplant from any donor source;
3. Subjects must have either:
- High risk CD34+ (positive) 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
- High risk CD34+ (positive) 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. Achievement of hematologic CR by day +60 post allo-HCT
5. Subject Karnofsky performance status must be >= 70
6. Neutrophil count >= 1.0 thou/mm3 and platelet count >= 50 thou/mm3
7. Subjects must have total bilirubin =8. Subjects must have serum AST and ALT levels =9. Subjects must have serum creatinine 30 ml/min by Cockcroft-Gault formula
10. Subjects must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of the REMS® program
11. Females of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program; and
- Written, voluntary informed consent, willingness, and ability to comply with all study procedures.

Exclusion Criteria:
1. CD34- (negative) AML or MDS
2. Inability to give informed consent
3. Absence of CR by day +60 after allo-HCT
4. Uncontrolled active infection(s) requiring intravenous antibiotics
5. Known or suspected hypersensitivity to lenalidomide
6. Grade II-IV acute GVHD or extensive GVHD
7. Not able to swallow the lenalidomide capsule as a whole
8. Female subjects who are pregnant or nursing.

Applicable Disease Sites
Leukemia
Myelodysplastic Syndrome (MDS)

Drugs Involved
Revlimid (Lenalidomide)

Participating Institutions
UF Gainesville : Christina Cline

Contact
Christina Cline, RN
Phone: +1 352-273-6840

Email: clcline@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02370888