UF-BMT-MRD-101: Lenalidomide After Allo-Hematopoietic Cell Transplant (HCT) in Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS) Subjects With Minimal Residual Disease

• Sponsor: University of Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02370888
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Actual Duration (Months): 36.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid; Myelodysplastic Syndromes	Drug: Lenalidomide	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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 (UF-BMT-MRD-101)
• Actual Study Start Date: May 16, 2016
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Lenalidomide will be administered for a total of 42 days. The dose levels of lenalidomide will be as follows: Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28-day cycle X 2 cycles Dose Level 2: 2.5 mg PO QD Day 1-21 for 28-day cycle X 2 cycles Dose Level 3: 5 mg PO QD Day 1-21 for 28-day cycle X 2 cycles Dose Level 4: 7.5 mg PO QD Day 1-21 for 28-day cycle X 2 cycles	Drug: Lenalidomide; 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.; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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:

4. 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

5. 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;

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

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

8. Subject Karnofsky performance status must be ≥ 70;

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

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

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

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

13. 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);

14. 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;

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

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

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32608

Sponsors and Collaborators

• University of Florida
• Celgene Corporation

Investigators

• Principal Investigator: Maxim N. Norkin, M.D., Ph.D, University of Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 25, 2017

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02370888
• Other Study ID Numbers: WIRB20151509; RV-CL-AML-PI-002987
• First Posted: Feb 25, 2015
• Last Update Posted: Jan 27, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Florida: Lenalidomide; Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation
• Additional relevant MeSH terms: Leukemia; Preleukemia; Neoplasm, Residual; Leukemia, Myeloid; Myelodysplastic Syndromes; Syndrome; Lenalidomide

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Dose Escalation of Lenalidomide
Arm/Group Description	Participants in the Arm only received Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28-day cycle X 2 cycles
Period Title: Overall Study
STARTED	9
Proceed to Treatment	3
COMPLETED	1
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Total
Arm/Group Description	2.5 mg PO QOD Day 1-21 for 28 day cycle X 2 Enrolled 3 subjects	2.5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles	5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles	7.5 mg PO QD Day 1-21 for 28 day cycle X 2 cycles	Total of all reporting groups
Overall Participants	3	0	0	0	3
Age, Customized (Count of Participants)
Count of Participants [Participants]	3 100%	3 Infinity
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 Infinity
Male	2 66.7%	2 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	3 100%	3 Infinity
Unknown or Not Reported	0 0%	0 NaN
Number of Participants with CD34 donor chimerism drop (Count of Participants)
Count of Participants [Participants]	3 100%	3 Infinity

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Lenalidomide
Description	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

Outcome Measure Data

Analysis Population Description

Cohort requirements for analysis not met. MTD could not be assessed as only a single dose level was tested. No dose escalation was performed.

Arm/Group Title	Dose Level 1
Arm/Group Description	Lenalidomide 2.5 mg by mouth every other day for twenty-one days of a 28 day cycle for 2 cycles.
Measure Participants	0

2. Secondary Outcome

Title	CD34+ Mixed Chimerism
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	Lenalidomide 2.5 mg by mouth every other day for twenty-one days of a 28 day cycle for two cycles.	Lenalidomide 2.5 mg by mouth daily for twenty-one days of a 28 day cycle for two cycles.	Lenalidomide 5 mg by mouth daily for twenty-one days of a 28 day cycle for 2 cycles.	Lenalidomide 7.5 mg by mouth daily for twenty-one days of a 28 day cycle for 2 cycles.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	9 months
Arm/Group Title	Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28 Day Cycle X 2
Arm/Group Description	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.
All Cause Mortality
	Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28 Day Cycle X 2
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28 Day Cycle X 2
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1: 2.5 mg PO QOD Day 1-21 for 28 Day Cycle X 2
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	2/3 (66.7%)	2
Gastrointestinal disorders
Gastrointestinal disorders	1/3 (33.3%)	5
General disorders
General disorders and administration site conditions	2/3 (66.7%)	4
Infections and infestations
Infections and infestations	1/3 (33.3%)	1
Investigations
Investigations	2/3 (66.7%)	18
Metabolism and nutrition disorders
Metabolism and nutrition disorders	2/3 (66.7%)	5
Nervous system disorders
Nervous system disorders	1/3 (33.3%)	2
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	2/3 (66.7%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.