Nonmyeloablative Haploidentical Transplant Followed by MLN9708
|ClinicalTrials.gov Identifier: NCT02169791|
Recruitment Status : Active, not recruiting
First Posted : June 23, 2014
Last Update Posted : May 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Leukemia Chronic Leukemia Myelodysplastic Syndrome Lymphomas Multiple Myeloma||Drug: MLN9708||Phase 2|
Overview of Study Design:
In an attempt to reduce relapse risk and improve outcomes following haploidentical transplantation for patients with high risk hematologic malignancies, the investigators will implement several strategies to augment the well documented effect of NK cell alloreactivity seen in HLA-mismatched transplantation. These strategies include (1) choosing potential haploidentical donors for optimal NK-alloreactivity, (2) utilizing proteasome inhibition post-transplant with MLN9708 to both sensitize tumor cells to NK cytotoxicity and protect against graft-versus-host disease (GVHD), and (3) eliminating mycophenolate mofetil from the post-transplant immunosuppression regimen to improve NK cell reconstitution following haploidentical peripheral blood stem cell transplantation.
Patients will receive a nonmyeloablative haploidentical transplant using a T-cell replete allograft and post-transplant cyclophosphamide as previously described at our center (Bashey et al. J Clin Oncol. 2013; 31(10):1310-6). MLN9708 will be administered once weekly for 3 weeks on a 28 day cycle for one-year post-transplant. Post-transplant immunosuppression will consist of tacrolimus only (MLN9708 will substitute for mycophenolate mofetil as the second GVHD prophylactic medication).
The primary endpoint of this trial will be the risk of relapse and/or progression at one-year post-transplant. Experience from the literature suggests that following a nonmyeloablative haploidentical transplant using post-transplant cyclophosphamide (haplo-pCy), the risk of relapse is approximately 50% at one year post-transplant. It is hoped that under this protocol, this rate will be at most 25%. Thus the investigators statistically formalize this study by testing the null hypothesis that p, the PFS rate is 0.25 or less versus the alternative hypothesis that p is greater than 0.5. A sample size of 25 patients gives 90% power with an alpha=0.05, using the formula for a one sample binomial (two-sided) test of a proportion.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation Followed By Maintenance Therapy With the Novel Oral Proteasome Inhibitor, MLN9708, in Patients With High-risk Hematologic Malignancies|
|Actual Study Start Date :||July 15, 2014|
|Estimated Primary Completion Date :||August 30, 2019|
|Estimated Study Completion Date :||August 30, 2020|
Experimental: Haploidentical Transplant
All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708.
MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
- Incidence of Relapse and progression [ Time Frame: 1 year ]To estimate the incidence of relapse/progression at one-year post-transplant.
- Overall Survival [ Time Frame: 3 years ]To obtain estimates of overall survival (OS)
- Event Free [ Time Frame: 3 years ]To obtain estimates of event-free survival (EFS)
- Non-relapsed mortality [ Time Frame: 3 years ]To obtain estimate of non-relapse mortality (NRM)
- Graft-versus-host disease [ Time Frame: 3 years ]To obtain estimates of acute and chronic graft-versus-host disease (GVHD).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02169791
|United States, Georgia|
|Atlanta, Georgia, United States, 30342|