Leukemia, Myeloid, Myelodysplastic Syndromes
Conditions
Keywords
Lenalidomide, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation
Brief summary
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.
Detailed description
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.
Interventions
DRUGLenalidomide
Subjects will be enrolled in cohorts of three (3). Lenalidomide will be administered for 21 consecutive days in a 28 day cycle X 2 cycles. The starting dose will be 2.5 mg given orally every other day for 21 days.
Sponsors
Celgene Corporation
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Lenalidomide | Up to 72 days | To determine safety and the maximum tolerated dose of lenalidomide after allo-HCT in AML and MDS subjects with MRD detected by the CD34+ mixed chimerism analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD34+ Mixed Chimerism | Up to 120 days | To monitor changes in the CD34+ mixed chimerism after allo-HCT in AML and MDS subjects with detectable MRD in response to escalating doses of lenalidomide. |
Countries
United States
Participant flow
Pre-assignment details
Per protocol, enrollment is completion of informed consent. 11 subjects were enrolled- 2 did not meet eligibility and 9 did. Of the 9 eligible subjects- 3 received protocol treatment assignment, 5 did not have their chimerism drop, per protocol, below 90% at day 60 or 90 post-transplant, and 1 withdrew consent prior to assignment.
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 2.5 mg PO QOD Day 1-21 for 28 day cycle X 2 Enrolled 3 subjects | 3 |
| Dose Level 2 2.5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles | 0 |
| Dose Level 3 5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles | 0 |
| Dose Level 4 7.5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles | 0 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | did not meet chimerism criteria | 6 |
| Overall Study | disease progression | 2 |
Baseline characteristics
| Characteristic | Dose Level 1 | Total |
|---|---|---|
| Age, Customized | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Number of Participants with CD34 donor chimerism drop | 3 Participants | 3 Participants |
| Sex: Female, Male Gender Female | 1 Participants | 1 Participants |
| Sex: Female, Male Gender Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Lenalidomide
To determine safety and the maximum tolerated dose of lenalidomide after allo-HCT in AML and MDS subjects with MRD detected by the CD34+ mixed chimerism analysis.
Time frame: Up to 72 days
Population: Cohort requirements for analysis not met. MTD could not be assessed as only a single dose level was tested. No dose escalation was performed.
Secondary
CD34+ Mixed Chimerism
To monitor changes in the CD34+ mixed chimerism after allo-HCT in AML and MDS subjects with detectable MRD in response to escalating doses of lenalidomide.
Time frame: Up to 120 days
Population: No participant met the requirements for the efficacy population (at least 21 days of the study drug and at least one post-cycle efficacy assessment). Therefore, no data were collected for this assessment.