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)

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid
• Intervention / Treatment: Drug: Lenalidomide

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Shands Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 72 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 120 days

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Maxim N. Norkin, M.D., Ph.D, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2016
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Lenalidomide; Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Neoplastic Processes; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Preleukemia; Neoplasm, Residual; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: WIRB20151509; RV-CL-AML-PI-002987 (Other Grant/Funding Number: Celgene Corporation)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No