Phase 2
Completed N=25
Nonmyeloablative Haploidentical Transplant Followed by MLN9708
Source: ClinicalTrials.gov NCT02169791 ↗Enrolled (actual)
25
Serious AEs
40.0%
Results posted
Sep 2021
Primary outcomePrimary: Number of Participants Experiencing Relapse or Progression — 10 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Experiencing Relapse or Progression |
10 | — |
| SECONDARY Neutrophil Engraftment |
16 | — |
| SECONDARY Time to Platelet Recovery Post Transplant |
29 | — |
| SECONDARY Day 30 CD3 Donor Chimerism |
100 | — |
| SECONDARY Day 30 CD33 Donor Chimerism |
100 | — |
| SECONDARY Graft Versus Host Disease |
28.5 | — |
Eligibility Criteria
Inclusion Criteria
- Availability of a 3/6 - 5/6 matched (HLA-A, B, DR) related donor
- Donor must have negative HLA cross-match in the host vs. graft direction.
- Donor must be willing to donate mobilized peripheral blood stem cells
- Age ≥ 18 years
- Karnofsky status ≥ 70%
- One of the following high-risk malignancies:
- Chronic Myelogenous Leukemia (chronic phase, resistant and/or intolerant to tyrosine kinase inhibitors (OR) accelerated phase (OR) blast crisis in 2nd chronic phase following induction chemotherapy)
- Acute Myelogenous Leukemia (2nd or subsequent complete remission [CR] (OR) Primary induction chemotherapy failure, but subsequently entered into a CR(OR) 1st CR with poor risk cytogenetics or molecular markers; or arising from preceding hematological disease)
- Myelodysplastic Syndrome (treatment-related, monosomy 7 or complex cytogenetics, IPSS score of 1.5 or greater, Chronic myelomonocytic leukemia [CMML])
- Acute lymphocytic leukemia/lymphoblastic lymphoma (2nd or subsequent CR (OR) Primary induction chemotherapy failure, but subsequently entered into a CR (OR) 1st CR with poor risk cytogenetics)
- Chronic Lymphocytic Leukemia / Prolymphocytic Leukemia (Duration of remission 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT > 3X ULN
- Poor renal function: Creatinine >2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) /= Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing
Data sourced from ClinicalTrials.gov (NCT02169791). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.