Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)

NCT01303965 | Terminated Phase 1 Results DMC

• 1 other identifier: 1012-24; IUCRO-0307
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

One of the complications that can occur after a stem cell transplant is called graft versus host disease (GVHD). Another complication is that multiple myeloma may come back (relapse). In this study, a drug called lenalidomide will be started 1-2 months after a transplant, or possibly later depending on recovery of your side effects. Lenalidomide and sirolimus have been shown to work together against multiple myeloma. Therefore, lenalidomide will be combined with sirolimus with the hope that this will help prolong the amount of time the disease is in remission. Researchers hope these steps will help prolong the amount of time the multiple myeloma is in remission and will decrease the chance of GvHD.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Phase I: Number of Participants With Dose Limiting Toxicity

  The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.

  28 days

• Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant

  Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be \>=0.5 g/dl, Urine M-protein and/or absolute increase must be \>=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++\>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.

  Transplant (Day 0) through 1 year post-transplant

Secondary Outcomes (6)

• Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)

  Day 0 through 1 year post transplantation

• Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)

  Transplant (Day 0) through 1 year post-transplant

• Phase II - Percent of Patients With Treatment-related Deaths at 100 Days

  100 days post transplant

• Phase II - Percent of Patients With Treatment-related Deaths at 1 Year

  Transplant (Day 0) through 1 year post-transplant

• Phase II - Time to Neutrophil Engraftment

  Transplant (Day 0) through 1 year post transplant

Study Arms (1)

Open Label, Single Arm

EXPERIMENTAL

Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance

Drug: Sirolimus; Drug: Tacrolimus; Drug: Lenalidomide

Interventions

Sirolimus DRUG

Start on Day -3 and continue for 1 year

Open Label, Single Arm

Tacrolimus DRUG

Start on Day -3 and begin tapering on Day +100 until Day +180.

Open Label, Single Arm

Lenalidomide DRUG

Start between Day +30 and +120 and continue for 1 year.

Open Label, Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Understand and voluntarily sign an informed consent form.
• \. Age 18-70 years at the time of signing the informed consent form.
• \. Able to adhere to the study visit schedule and other protocol requirements.
• \. Previously documented multiple myeloma (MM) with measurable monoclonal protein by either serum/urine protein electrophoresis or serum free light chains, or measurable plasmacytomas.
• \. ECOG performance status of 0-2 at study entry (see Appendix 2).
• \. Acceptable organ function as outlined in the protocol.
• \. Otherwise fitting institutional criteria for allogeneic stem cell transplantation.
• \. Presence of an HLA-matched (5/6 or 6/6 matched for HLA-A, B, and DR) sibling donor, or a HLA-matched (matched for at least HLA-A, B, C, and DRB1) unrelated donor by high-resolution testing.
• \. Disease free of prior malignancies for \>/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
• \. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• \. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test

You may not qualify if:

• \. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• \. Pregnant or breast feeding females.
• \. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• \. Known hypersensitivity to thalidomide or Lenalidomide.
• \. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• \. Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or prior infection to which they are now immune (i.e., not carriers) are eligible.
• The following categories of donor will be acceptable:
• \. HLA-matched related donor (5/6 or 6/6 match): Minimal typing necessary is serologic typing for class I (A, B) and molecular typing for class II (DRB1).
• \. HLA-matched Unrelated Donor (MUD): Molecular identity at least at HLA A, B, C, and DRB1 and DQB1 (8/10 match) by high resolution typing is required.
• \. Syngeneic donors are not eligible.
• \. The donor must be healthy and must be an acceptable donor as per institutional standards for marrow or stem cell donation.
• \. Age ≥ 18 years

Sponsors & Collaborators

• Sherif S. Farag: lead
• Celgene Corporation: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Sirolimus; Tacrolimus; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Sherif Farag
• Organization: IndianaU

ssfarag@iu.edu

(317) 278-0460

Study Officials

• Sherif Farag, MD, PhD

  IU Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: February 25, 2011
• Study Start: February 7, 2011
• Primary Completion: September 23, 2014
• Study Completion: July 28, 2017
• Last Updated: January 8, 2019
• Results First Posted: December 6, 2018

Record last verified: 2018-12

Locations

US (1)