Phase 1a/1b study of Itacitinib (INCB039110) for cytokine release syndrome prevention and minimization of immunosuppression following nonmyeloablative related partially HLA-mismatched peripheral blood stem cell transplant (PBSCT) with high-dose posttransp
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
I
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Keywords
Contact Us
(410) 955-8964Brief Summary
The study will be completed in two stages: Phase 1a, the dose (regimen) finding stage that will examine 4 different dose levels (regimens), and Phase 1b, where the dose and study drug administration schedule determined in the first stage will be given. Approximately 12-24 participants will be enrolled in each stage, for a total of up to 32 participants between both phases. Itacitinib will be started 3 days before transplant to prevent CRS and continued for 90 days after transplant.
Eligibility
Inclusion Criteria:
Presence of a suitable related, HLA-haploidentical (partially mismatched) stem cell donor.
Eligible diagnoses:
- Acute leukemias in complete remission with minimal residual disease
- Myelodysplastic syndrome (MDS) with at least one poor-risk feature
- Chronic myelomonocytic leukemia with at least one poor-risk feature
- T-cell PLL in PR or better prior to transplantation.
- Tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase.
- Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
- Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen
Age ≥ 60 years.
Adequate end-organ function as measured by:
- Left ventricular ejection fraction ≥ 35% or shortening fraction > 25%
- Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN
- FEV1 and FVC ≥ 40% of predicted
ECOG performance status ≤ 2 or Karnofsky score ≥ 60
Exclusion Criteria:
- No active extramedullary leukemia or known active CNS involvement by malignancy.
- Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning.
- No previous allogeneic HSCT.
- Not pregnant or breast-feeding
- No uncontrolled infection.
- No known HIV infection.
- No active replicating HBV or HCV infection detected by PCR that requires treatment or at risk for HBV reactivation (positive HBsAg)