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

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sirolimus

Tacrolimus

Lenalidomide

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Indiana University Melvin and Bren Simon Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label, Single Arm

Arm Description

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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

Percent of patients and the 95% Binomial Confidence interval who had any stage I-IV acute GvHD based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms for patients in Phase II. Zero means no acute GvHD was reported, and higher stages are worse outcomes (range of 0-4). For skin: 0=no rash; 1=erthematous macular rash over <25% body surface; 2=over 25-50% of body surface; 4=bullae, exfoliation ulcerative dermatitis. For liver (bilirubin (mg/dL)): 0= <2.0; 1= 2-<2.9; 3= 3-<5.9; 4= >=15 . For gut changes (diarrhea[ml/day]): 0=none; 1= >500-1000; 2= >1000-1500; 3= >1500; 4=severe abdominal pain with or without ileus. Overall grade 0: Skin=0; liver=0; gut changes=0. Overall grade 1: Skin with 1 or 2; liver=0; gut changes=0. Overall grade 2: Skin with 1, 2, or 3; liver=1; gut changes=1. Overall grade 3: Skin with 2 or 3; liver with 2 or 3; gut changes with 2 or 3. Overall grade 4: Patients with grade 4 toxicity in any organ system.

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

Percent of patients and the 95% Binomial Confidence interval who had any chronic GvHD reported based on Filipovich et al. consensus document (BB&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003) for patients in Phase II.

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

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 100 days for patients in Phase II.

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

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 1 year for patients in Phase II.

Phase II - Time to Neutrophil Engraftment

Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.

Phase II - Time to Platelet Engraftment

Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.

Full Information

NCT ID

NCT01303965

First Posted

February 18, 2011

Last Updated

December 17, 2018

Sponsor

Sherif S. Farag

Collaborators

Celgene Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01303965

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Terminated

Why Stopped

Slow accrual

Study Start Date

February 7, 2011 (Actual)

Primary Completion Date

September 23, 2014 (Actual)

Study Completion Date

July 28, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sherif S. Farag

Collaborators

Celgene Corporation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open Label, Single Arm

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Intervention Description

Start on Day -3 and continue for 1 year

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Intervention Description

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

Primary Outcome Measure Information:

Title

Phase I: Number of Participants With Dose Limiting Toxicity

Description

Time Frame

28 days

Title

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

Description

Time Frame

Transplant (Day 0) through 1 year post-transplant

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Day 0 through 1 year post transplantation

Title

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

Description

Time Frame

Transplant (Day 0) through 1 year post-transplant

Title

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

Description

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 100 days for patients in Phase II.

Time Frame

100 days post transplant

Title

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

Description

Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 1 year for patients in Phase II.

Time Frame

Transplant (Day 0) through 1 year post-transplant

Title

Phase II - Time to Neutrophil Engraftment

Description

Time Frame

Transplant (Day 0) through 1 year post transplant

Title

Phase II - Time to Platelet Engraftment

Description

Time Frame

Transplant (Day 0) through 1 year post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sherif Farag, MD, PhD

Organizational Affiliation

IU Simon Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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