Momelotinib During and After HCT in Myelofibrosis

NCT07104799 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-501
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Myelofibrosis; Hematopoietic Cell Transplantation (HCT)

Keywords

myelofibrosis; allogeneic hematopoietic cell transplantation (HCT); HCT

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of study treatment (Day -7) through 28 days.

Secondary Outcomes (12)

• Incidence of momelotinib-related toxicities

  Day -7 through 30 days after end of treatment (up to 394 days)

• Median Duration of Momelotinib Therapy

  Day -7 through end of treatment, up to 364 days.

• Median time to neutrophil engraftment

  Day 0 (Day of HCT) through Day 60.

• Median time to platelet engraftment

  Day 0 (Day of HCT) through Day 60.

• Time to red blood cell transfusion independence

  Day 0 through end of treatment, up to 1 year.

Study Arms (1)

Momelotinib + Standard of Care (SOC) Hematopoietic Cell Transplantation (HCT)

EXPERIMENTAL

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

Interventions

Momelotinib DRUG

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

Momelotinib + Standard of Care (SOC) Hematopoietic Cell Transplantation (HCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have pathologically confirmed primary myelofibrosis (PMF) according to WHO criteria or secondary myelofibrosis as defined by the IWG-MRT criteria.
• Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) Plus criteria OR
• Intermediate-1 risk disease with at least one of the following unfavorable features known to impact the survival adversely
• Red cell transfusion dependency
• Unfavorable Karyotype
• Platelet count ≤100 x 10\^9/L
• Presence of a high risk molecular marker associated with worsened overall survival (ASXL1, EZH2, IDH1/2, SRSF2, U2AF1, p53)
• Participants do not have to be receiving treatment with JAK inhibitors for MF at the time of enrollment. If participants are receiving JAK inhibitor therapy with agents other momelotinib, participants must agree to be switched to momelotinib to begin Cycle 1 Day 1 on Day -7 from HCT (at the initiation of conditioning).
• Age \>18 years
• Participants must be designated to undergo allogeneic HCT with:
• reduced intensity conditioning regimen, and
• peripheral blood stem cells as a graft source
• Participants who will undergo HCT from the following donor types are eligible:
• /6 (HLA-A, B, DR) fully matched related donor or
• /8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level

You may not qualify if:

• \- Ability to understand and the willingness to sign a written informed consent document.
• Known intolerance or hypersensitivity to any JAK inhibitor, including ruxolitinib, fedratinib, pacritinib, momelotinib or any other JAK inhibitor, its metabolites or formulation excipients.
• Has had any major surgery within 28 days prior to randomization
• Has received treatment with an investigational agent within 4 weeks of the first dose of study intervention
• Has received immunosuppressive agents within 28 days
• Prior allogeneic transplant for any hematopoietic disorder
• Had accelerated phase or leukemic transformation (≥10% blasts in bone marrow any time prior to HCT)
• Has an active, uncontrolled infection
• Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
• Known diagnosis of active hepatitis B or hepatitis C.
• History of another malignancy(ies), unless:
• the participant has been disease-free for at least 2 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
• the cancer has been deemed indolent with no progression over the last 2 years, and deemed by the investigator to be at low risk for further progression during the course of study and follow-up
• the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
• Participants without normal organ function defined as follows:

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gabriela Hobbs, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gabriela Hobbs, MD

CONTACT

(617) 726-8748; ghobbs@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: February 23, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)