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

Primary Purpose

Leukemia, Myeloid, Myelodysplastic Syndromes

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid focused on measuring Lenalidomide, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Florida Shands Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
February 10, 2015
Last Updated
January 13, 2020
Sponsor
University of Florida
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02370888
Brief Title
Lenalidomide After Allo-Hematopoietic Cell Transplant (HCT) in Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS) Subjects With Minimal Residual Disease
Acronym
UF-BMT-MRD-101
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
May 16, 2016 (Actual)
Primary Completion Date
May 31, 2019 (Actual)
Study Completion Date
May 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
Celgene Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Myelodysplastic Syndromes
Keywords
Lenalidomide, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention 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. The starting dose will be 2.5 mg given orally every other day for 21 days.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must be at least 18 years of age; Subjects must be post-allogeneic transplant from any donor source; Subjects must have either: 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 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; For AML subjects, they must have a documented CR within 45 days prior to allo-HCT; For MDS subjects, they must have < 20% myeloblasts in the bone marrow within 45 days prior to allo-HCT; Subject Karnofsky performance status must be ≥ 70; Subjects must be platelet transfusion independent (Platelet transfusion independence is defined as 7 days or greater without a platelet transfusion); Neutrophil count ≥ 1.0 thou/mm3 and platelet count ≥ 30 thou/mm3; Subjects must have total bilirubin ≤ 2 mg/dL; Subjects must have serum AST and ALT levels ≤ 2.5 times upper limit of normal; 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); 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; 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 Written, voluntary informed consent, willingness, and ability to comply with all study procedures. Exclusion Criteria: CD34- AML or MDS; Inability to give informed consent; Uncontrolled active infection(s) requiring intravenous antibiotics; Known or suspected hypersensitivity to lenalidomide; Grade II-IV acute GVHD or extensive GVHD; Not able to swallow the lenalidomide capsule as a whole; Female subjects who are pregnant or nursing.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maxim N. Norkin, M.D., Ph.D
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida Shands Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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