A Phase 1 interventional study of Momelotinib in Myelofibrosis and Hematopoietic Cell Transplantation (HCT), sponsored by Massachusetts General Hospital. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-31.
Sponsored by Massachusetts General Hospital · Phase 1, Interventional, and Treatment
This is a single-center, open-label, phase I study to determine the safety and tolerability of momelotinib in patients with myelofibrosis during and after hematopoietic cell transplantation (HCT).
The purpose of this study is to test the safety, effects, and recommended dose of an investigational drug, momelotinib, during and after undergoing allogeneic HCT. This study will enroll up to 28 participants with myelofibrosis that are planned to undergo standard of care allogeneic hematopoietic cell transplantation (HCT). Participants may receive momelotinib or other JAK inhibitors prior to HCT and may adjust momelotinib dosing per protocol as follows: Multiple dose cohorts (100 mg daily, 150 mg daily and 200 mg daily) will be investigated in the peri-transplant period. Participants not previously on momelotinib will begin this drug at the initiation of conditioning therapy (Day -7 from HCT). Once participants have achieved hematopoietic recovery and are at least Day 21(cycle 2 day 1) after HCT, participants, receiving lower doses will increase the dose to 200 mg daily. Patients will remain on momelotinib for a total of 13 cycles (28 days per cycle, until approximately 1 year after transplant). After HCT, participants will be followed for up to 2 years.
419 studies on the registry are indexed under Primary Myelofibrosis; 117 are open to participants now.
This study's planned enrollment of 28 is below the median of 44 across 347 interventional studies indexed under Primary Myelofibrosis.
Browse Primary Myelofibrosis studies →Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.
Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants must have pathologically confirmed primary myelofibrosis (PMF) according to WHO criteria or secondary myelofibrosis as defined by the IWG-MRT criteria.
Intermediate-1 risk disease with at least one of the following unfavorable features known to impact the survival adversely
Participants must be designated to undergo allogeneic HCT with:
Participants who will undergo HCT from the following donor types are eligible:
Male participants with women of child bearing potential partners must agree to use one of the forms of medically acceptable birth control at start of the first treatment, during the study, and for at least 6 months after the last dose. See Exclusion Criteria for effective contraception and birth control.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
History of another malignancy(ies), unless:
Participants without normal organ function defined as follows:
To exclude women of childbearing potential: who are unwilling or unable to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 1 week after the last dose. Highly effective contraceptive measures include:
To exclude sexually active male participants with WOCBP partners who are unwilling to use the one of the following forms of medically acceptable birth control at start of the first treatment, during the study, and for at least 6 months after the last dose:
Momelotinib will be administered orally once daily at a pre-determined dose starting 7 days before standard of care (SOC) hematopoietic cell transplantation (HCT) and for up to 1 year after HCT, for a total of 13 28-day cycles. Participants will receive SOC HCT and HCT treatment including: reduced intensity conditioning (RIC) regimen before HCT (Fludarabine, Mephalan), and tacrolimus and methotrexate after HCT, all administered according to SOC.
Drug: Momelotinib
Administered orally once per day during each 28-day cycle. This will start on day -7 (7 days before HCT) and continue for up to 13 cycles. Dose cohorts (100 mg daily, 150 mg daily, 200 mg daily) will be investigated in the peri-transplant period. Once participants have achieved hematopoietic recovery and are at least Day 21 after HCT, participants will increase the dose to 200 mg daily.
Also known as: GSK3070785
Maximum Tolerated Dose (MTD) of Momelotinib
MTD is defined as the highest dose level at which 0 or 1 of 6 patients experience a Dose Limiting Toxicity (DLT). Toxicities will be graded and documented according to NCI CTCAE version 5.0.
Time frame: From start of study treatment (Day -7) through 28 days.
Incidence of momelotinib-related toxicities
Toxicity will be categorized and graded per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria.
Time frame: Day -7 through 30 days after end of treatment (up to 394 days)
Median Duration of Momelotinib Therapy
Median duration of momelotinib therapy during and after allogeneic HCT will be calculated and is the duration of study treatment which divides the shortest 50% and longest 50% of treatment durations.
Time frame: Day -7 through end of treatment, up to 364 days.
Median time to neutrophil engraftment
Neutrophil engraftment will be defined as first of 3 successive days with an absolute neutrophil count of greater than or equal to 0.5 x 10\^9/l after post-HCT nadir. Median time to neutrophil engraftment for participants receiving momelotinib during allogeneic HCT will be calculated.
Time frame: Day 0 (Day of HCT) through Day 60.
Median time to platelet engraftment
Platelet engraftment will be defined as first of 3 successive days with platelet count of greater than or equal to 20 x 10\^9/l in the absence of platelet transfusion for 7 consecutive days. Median time to platelet engraftment for participants receiving momelotinib during allogeneic HCT will be calculated.
Time frame: Day 0 (Day of HCT) through Day 60.
Time to red blood cell transfusion independence
Transfusion independence is defined as clinical hematologic recovery requiring no transfusion in the past 7 days. The time from Day 0 to transfusion independence will be reported.
Time frame: Day 0 through end of treatment, up to 1 year.
Cumulative incidence of primary graft failure
Primary graft failure will be defined as lack of achievement of an absolute neutrophil count of greater than or equal to 0.5 x 10\^9/l by Day +30 after HCT with associated pancytopenia. Incidence of primary graft failure in participants receiving momelotinib during and after allogeneic HCT will be reported.
Time frame: Day 0 through Day 60.
Cumulative incidence of acute graft-versus-host disease (GVHD)
Clinical stage and grade of acute graft-versus-host-disease (GVHD) is based on MAGIC Criteria. The incidence of acute GVHD grade II-IV and grade III-IV will be estimated for each treatment group using the cumulative incidence estimate, treating death prior to acute GVHD as a competing event. Incidence of acute GVHD in participants receiving momelotinib during and after allogeneic HCT will be reported.
Time frame: Day 0 through 2 years after HCT
Cumulative incidence of chronic graft-versus-host disease (GVHD)
Chronic GVHD will be assessed as per the 2014 National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. The incidence of chronic GVHD will be estimated for each treatment group using the cumulative incidence estimate, treating death prior to chronic GVHD as a competing event.
Time frame: Day 0 through 2 years after HCT
Incidence of Non-relapse mortality (NRM)
Clinical response is evaluated using the using the Revised IWG-MRT, ELN response criteria for Myelofibrosis, and recently defined endpoints for MF based on recently defined consensus criteria. The incidence of non-relapse mortality (NRM) will be estimated for each treatment group using the cumulative incidence estimate, treating disease relapse or progression as a competing event. NRM will be estimated in the context of a competing risks framework. Gray test will be used for group comparison of cumulative incidence of NRM.
Time frame: Day -7 through 2 years post HCT.
Progression-free survival (PFS)
Clinical response is evaluated using the using the Revised IWG-MRT, ELN response criteria for Myelofibrosis, and recently defined endpoints for MF based on recently defined consensus criteria. Progression-free survival is defined as the time from first dose of study drug to the earlier of disease relapse or death due to any cause. Participants alive and progression-free are censored at the date of last disease evaluation.
Time frame: Day -7 through 2 years post HCT.
Overall survival (OS)
Overall Survival is defined as the time from first dose of study drug to the date of death due to any cause. Participants who are alive at the analysis / cutoff date will be censored at the last contact date. OS will be estimated using the Kaplan-Meier method and compared using log-rank test.
Time frame: Day -7 through 2 years post HCT.
GVHD-free, relapse-free survival (GRFS)
GVHD, relapse-free survival is defined as the time from first dose of study drug to the earlier of grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, leukemia relapse or death due to any cause. Participants alive and without one of these three events are censored at the date of last disease evaluation. GRFS will be estimated using the Kaplan-Meier method and compared using log-rank test.
Time frame: Day -7 through 2 years post HCT
Plan to share: Yes — The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Gabriela Hobbs, MD, ghobbs@mgb.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting information: Study protocol, Sap, Icf
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