Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)
|ClinicalTrials.gov Identifier: NCT01303965|
Recruitment Status : Terminated (Slow accrual)
First Posted : February 25, 2011
Results First Posted : December 6, 2018
Last Update Posted : January 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Sirolimus Drug: Tacrolimus Drug: Lenalidomide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||February 7, 2011|
|Actual Primary Completion Date :||September 23, 2014|
|Actual Study Completion Date :||July 28, 2017|
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.
- Phase I: Number of Participants With Dose Limiting Toxicity [ Time Frame: 28 days ]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 [ Time Frame: Transplant (Day 0) through 1 year post-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.
- Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD) [ Time Frame: Day 0 through 1 year post transplantation ]
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) [ Time Frame: Transplant (Day 0) through 1 year post-transplant ]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 [ Time Frame: 100 days post transplant ]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 [ Time Frame: Transplant (Day 0) through 1 year post-transplant ]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 Frame: Transplant (Day 0) through 1 year post transplant ]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 Frame: Transplant (Day 0) through 1 year post-transplant ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01303965
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Sherif Farag, MD, PhD||IU Simon Cancer Center|