Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Sherif S. Farag, Indiana University
First received: February 18, 2011
Last updated: March 14, 2016
Last verified: March 2016
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.
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma
Primary Outcome Measures:
- Number of Participants with Dose Limiting Toxicities as a Measure of Safety of the combination of sirolimus, tacrolimus and lenalidomide [ Time Frame: 1 year post transplantation ] [ Designated as safety issue: Yes ]
Determine the safety of reduced-intensity allogeneic stem cell transplantation using sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance in an initial Phase I component of the study
- Percent of patients alive and free of progression at 12 months. [ Time Frame: baseline through 1 year post-transplant ] [ Designated as safety issue: No ]
Determine if reduced-intensity allogeneic stem cell transplantation using sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance can result in 60% of patients with MM alive and free of progression at 12 months, with less than 40% considered unacceptable. This will be completed through the Phase II component of the study.
Secondary Outcome Measures:
- Number of subjects with acute and chronic Graft versus Host Disease (GvHD) [ Time Frame: Day 0 through 1 year post transplantation ] [ Designated as safety issue: No ]
Acute GvHD will be based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms (stage 0-4 for each organ).
Chronic GvHD will be based on Filipovich et al. consensus document (BB&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003).
- Number of treatment-related deaths at 100 days and 1 year [ Time Frame: Day +100 and 1 year post transplant ] [ Designated as safety issue: No ]
- Percentage of donor chimerism as assessed at days +30, +90, +180 and at 12 months post transplant [ Time Frame: +30, +90, +180 and 12 months post transplant ] [ Designated as safety issue: No ]
- Number of toxicities, frequency and type of infections occurring within the first year [ Time Frame: Day 0 through 1 year post transplantation ] [ Designated as safety issue: Yes ]
Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Time to engraftment of neutrophils and platelets [ Time Frame: baseline through engraftment ] [ Designated as safety issue: No ]
Engraftment is defined as an absolute neutrophil count (ANC) >/=0.5 x 10^9/L for three consecutive days.
- Time from day 0 to disease progression or death (regardless of cause of death), whichever comes first. [ Time Frame: Day 0 until disease progression ] [ Designated as safety issue: No ]
- Number of patients with disease progression [ Time Frame: Day 0 until disease progression ] [ Designated as safety issue: No ]
- Time from day 0 to death from any cause [ Time Frame: Day 0 until death ] [ Designated as safety issue: No ]
- Number of complete responses (CR), stringent complete responses (sCR), near complete responses (nCR), very good partial responses (VGPR), partial responses (PR) and minimal responses (MR). [ Time Frame: Day 0 until disease progression ] [ Designated as safety issue: No ]
Responses will be based on to International Myeloma Working Group criteria (Durie et al 2006)
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2016 (Final data collection date for primary outcome measure)
Experimental: Open Label, Single Arm
Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance
Start on Day -3 and continue for 1 year
Start on Day -3 and begin tapering on Day +100 until Day +180.
Start between Day +30 and +120 and continue for 1 year.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Recipient Inclusion Criteria:
- 1. Understand and voluntarily sign an informed consent form.
- 2. Age 18-70 years at the time of signing the informed consent form.
- 3. Able to adhere to the study visit schedule and other protocol requirements.
- 4. Previously documented multiple myeloma (MM) with measurable monoclonal protein by either serum/urine protein electrophoresis or serum free light chains, or measurable plasmacytomas.
- 5. ECOG performance status of 0-2 at study entry (see Appendix 2).
- 6. Acceptable organ function as outlined in the protocol.
- 7. Otherwise fitting institutional criteria for allogeneic stem cell transplantation.
- 8. 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.
- 9. 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.
- 10. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- 11. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
Recipient Exclusion Criteria:
- 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- 2. Pregnant or breast feeding females.
- 3. 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.
- 4. Known hypersensitivity to thalidomide or Lenalidomide.
- 5. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- 6. 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.
Donor Inclusion Criteria:
The following categories of donor will be acceptable:
- 1. 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).
- 2. 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.
- 3. Syngeneic donors are not eligible.
- 4. The donor must be healthy and must be an acceptable donor as per institutional standards for marrow or stem cell donation.
- 5. Age ≥ 18 years
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01303965
|Indiana University Melvin and Bren Simon Cancer Center
|Indianapolis, Indiana, United States, 46202 |
Sherif S. Farag
||Sherif Farag, MD, PhD
||IU Simon Cancer Center
||Sherif S. Farag, Professor of Medicine, Indiana University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 18, 2011
||March 14, 2016
||United States: Institutional Review Board
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 23, 2016
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Blood Protein Disorders
Immune System Diseases
Physiological Effects of Drugs
Angiogenesis Modulating Agents