CSF-1R Inhibitor, Axatilimab, for Prevention of Acute and Chronic GVHD After HLA-Matched Related and Unrelated Donor Allogeneic Stem Cell Transplantation

NCT07808112 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT-HAMADANI-ABRAXAS
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, multisite, Phase II study designed to compare the 1-year GVHD-free survival of the control arm (no axatilimab) to the experimental arm (axatilimab) after myeloablative allogeneic HCT.

Conditions

Graft -Versus-host-disease

Keywords

hematologic malignancy; myeloablative allogeneic hematopoietic cell transplantation

Outcome Measures

Primary Outcomes (1)

• GVHD-free survival

  A patient will be considered a success for 1-year GVHD-free survival if they are alive without Grade 3 or 4 acute GVHD or systemic immunosuppression requiring chronic GVHD at one year post transplant. Death, Grade 3 or 4 acute GVHD, and immunosuppression-requiring chronic GVHD (of any severity) prior to 1 year will be considered as events.

  1 Year Post HCT

Study Arms (3)

Safety Run-in

EXPERIMENTAL

An early safety analysis will be performed after the first 6 evaluable patients have been accrued to Dose Level 1 of the study and observed for four cycles of axatilimab (Cycles 1-4). Accrual will be temporarily halted while these patients are evaluated. If 2 or more of the first 6 patients experience a significant toxicity, then the protocol may be amended and the dose of axatilimab may be de-escalated to Dose Level -1.

Procedure: Hematopoietic Cell Transplantation; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Drug: Axatilimab

Axatilimab Treatment

EXPERIMENTAL

Starts 35 (±5) days from stem cell transplant; Dosing will occur every 14 days for a maximum of 12 cycles.

Procedure: Hematopoietic Cell Transplantation; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Drug: Axatilimab

No Axatilimab Treatment

EXPERIMENTAL

Starts 35 (±5) days from stem cell transplant.

Procedure: Hematopoietic Cell Transplantation; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF)

Interventions

Cyclophosphamide DRUG

Cyclophosphamide will be given on Day +3 and Day +4 per institutional practices, at a dose of 50 mg/kg IBW. Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume), or according to institutional standards.

Also known as: Cytoxan, Neosar, cytophosphane

Axatilimab Treatment; No Axatilimab Treatment; Safety Run-in

Tacrolimus DRUG

Tacrolimus will be given per institutional practices, starting on Day +5. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-12 ng/mL.

Axatilimab Treatment; No Axatilimab Treatment; Safety Run-in

Axatilimab DRUG

The dose is dependent on the results of the safety run-in. The starting dose of the safety run-in is 0.3 mg/kg (maximum of 35 mg). If Dose Level 1 has an unacceptable level of toxicity (≥2 patients having significant toxicity), then axatilimab may be de-escalated to 0.2 mg/kg (maximum of 23 mg).

Also known as: Niktimvo, axatilimab-csfr

Axatilimab Treatment; Safety Run-in

Hematopoietic Cell Transplantation PROCEDURE

Subjects will receive a first HLA-matched related or (7/8 or 8/8) unrelated donor myeloablative allogeneic HCT.

Axatilimab Treatment; No Axatilimab Treatment; Safety Run-in

Mycophenolate Mofetil (MMF) DRUG

Mycophenolate mofetil (MMF) will be given per institutional practices, at a dose of 15 mg/kg three times daily (TID; based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and continue until Day +35 post-transplant, at which time it should be discontinued (no taper necessary).

Axatilimab Treatment; No Axatilimab Treatment; Safety Run-in

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Patients with a history of a hematologic malignancy with a planned myeloablative conditioning (MAC) peripheral blood allogeneic HCT.
• a. Note: Patients with acute leukemia must be in morphologic complete remission with or without hematologic recovery with ≤5% blasts in the bone marrow. Patients with Chronic Myelomonocytic Leukemia (CMML) must have a white blood cell (WBC) count ≤10,000 cells/µL and ≤5% blasts in the marrow. Patients with ≥5% blasts due to a regenerating marrow must contact the protocol chairs for review. Patients with a diagnosis of myelofibrosis require sponsor approval before enrolling.
• Patients must be receiving an allograft from a suitable HLA-matched sibling or (7/8 or 8/8) unrelated donor according to transplant center's guidelines (for selection of appropriate donor).
• The following laboratory values obtained ≤14 days prior to registration/randomization:
• Total bilirubin ≤1.5 x ULN or total bilirubin ≤3.0 x the Upper Limit of Normal (ULN) in the presence of Gilbert's syndrome. If total bilirubin is abnormal (≥1.5 x ULN), assess direct bilirubin. NOTE: Patients with Gilbert Syndrome and elevated baseline unconjugated (indirect) bilirubin up to 3.0 mg/dL are eligible. Gilbert syndrome should be confirmed by the presence of UGT1A1\*28 variant.
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤2.5 x ULN).
• Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula below:
• Creatinine clearance for males = (140 - age)(weight in kg) /(72)(serum creatinine in mg⁄dL) Creatinine clearance for females = (140 - age)(weight in kg) (0.85) /(72)(serum creatinine in mg⁄dL)
• Negative serum pregnancy test done ≤7 days prior to registration/randomization, for persons of childbearing potential only.
• Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry and for the duration of study participation and for at least 3 months after the last dose of study drug.
• a. Note: The following are considered effective contraceptives: oral contraceptive pill; condom plus spermicide; diaphragm plus spermicide; patient or partner surgically sterile; patient or partner more than 12 months postmenopausal; or injectable or implantable agent/device. Male patients should refrain from sperm donation and female patients should refrain from breastfeeding throughout this period.
• Ability to understand and provide written informed consent at the time of initial study enrollment. Participants who later lose decisional capacity may remain on study with consent from a legally authorized representative (LAR), as applicable.
• Willingness to provide mandatory blood and bone marrow aspirate specimens for correlative research.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effect on the developing fetus and newborn are unknown:
• Pregnant persons.
• Nursing persons.
• Persons of childbearing potential, and persons able to father a child, who are unwilling to employ adequate contraception.
• Any of the following current or prior therapies:
• Patients receiving a cord blood transplant.
• Patients undergoing a T-cell depleted allogeneic transplantation (using ex vivo CD34 selection, or with serotherapy \[antithymocyte globulin or alemtuzumab\]).
• Patients undergoing a second allogeneic transplant (after a previous allogeneic transplant).
• Pre-planned treatment with JAK1/JAK2 inhibitor after transplant.
• Previous exposure to axatilimab.
• Receiving an investigational treatment ≤28 days prior to registration/randomization.
• Major surgery ≤3 weeks prior to registration/randomization.
• Chemotherapy ≤2 weeks prior to registration/randomization unless chemotherapy is part of the pre-transplant conditioning.
• Radiation therapy ≤2 weeks prior to registration/randomization unless radiation is part of the pre-transplant conditioning.
• Planned use of Donor Lymphocyte Infusion (DLI) therapy.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Interventions

Stem Cell Transplantation; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; axatilimab

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Mehdi Hamadani, MD

  Medical College of Wisconsin

  STUDY CHAIR

• Sameem Abedin, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: September 8, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)