Ruxolitinib With Tacrolimus and Methotrexate for the Prevention of Graft Versus Host Disease in Pediatric and Young Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

NCT06128070 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 23010NCI-2023-07401P30CA033572
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well ruxolitinib with tacrolimus and methotrexate work to prevent the development of graft versus host disease in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Ruxolitinib is a type of medication called a kinase inhibitor. It works by blocking the signals of cells that cause inflammation and cell proliferation, which may help prevent graft versus host disease (GVHD). Tacrolimus is a drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants by suppressing the immune system. Methotrexate stops cells from making DNA, may kill cancer cells, and also suppress the immune system, which may reduce the risk of GVHD. Giving ruxolitinib with tacrolimus and methotrexate may prevent GVHD in pediatric and young adults undergoing allogeneic hematopoietic cell transplants.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Defined using the modified Bearman Scale and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale.

  Up to day +30 post hematopoietic cell transplant (HCT)

• Graft-versus-host disease (GVHD)-free and relapse-free (GRFS)

  Will be estimated using the product-limit method of Kaplan and Meier.

  From the date of transplantation to the first time of observing the following events: grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death, assessed at 1 year post transplantation

Secondary Outcomes (14)

• Patients receiving planned doses of ruxolitinib (feasibility)

  At completion of therapy (up to day+100)

• Incidence of acute GVHD

  At 100 days post HCT transplant

• Incidence of non-relapse mortality

  At 100 days post HCT transplant

• Incidence of chronic GVHD

  At 1 and 2 years post HCT transplant

• Overall survival

  From the day of stem cell infusion until death, up to 2 years

Study Arms (1)

Prevention (Ruxolitinib, tacrolimus, methotrexate)

EXPERIMENTAL

Patients receive ruxolitinib PO BID from day -1 to day +100, tacrolimus IV on day -1, and methotrexate IV on days +1, +3, +6, and +11, and undergo HCT on day 0. Patients also undergo chest CT and ECHO/MUGA at screening and undergo collection of blood samples throughout the trial.

Procedure: Biospecimen Collection; Procedure: Chest Computed Tomography; Procedure: Echocardiography; Procedure: Hematopoietic Cell Transplantation; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ruxolitinib Phosphate; Drug: Tacrolimus

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Chest Computed Tomography PROCEDURE

Undergo chest CT

Also known as: Chest CT, Computed Tomography of the Chest

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT, SCT, Stem Cell Transplant, stem cell transplantation, Stem Cell Transplantation, NOS

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Ruxolitinib Phosphate DRUG

Given PO

Also known as: INCB-18424 Phosphate, Jakafi, Jakavi

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Tacrolimus DRUG

Given IV

Also known as: FK 506, FK-506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Prevention (Ruxolitinib, tacrolimus, methotrexate)

Eligibility Criteria

• Age: 2 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study primary investigator (PI) approval
• Age: 2-22
• Weight ≥25kg
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Performance status: Karnofsky ≥ 60% for patients ≥ 16 years old OR Lansky status ≥ 60% for patients \< 16 years old
• Candidate for allogeneic bone marrow transplant with and available matched related donor (MRD) or an 8/8 matched unrelated donor (MUD) who is willing to donate bone marrow (BM) or mobilized peripheral blood stem cells
• Note: Donor selection process will be in accordance with City of Hope (COH)-standard operating procedures (SOPs) (B.001.09 Allogeneic Cellular Therapy Product Donor Evaluation, Selection \& Consent), which follows Food and Drug Administration (FDA) guidelines for donation of hematopoietic stem/progenitor cells (HPCs) obtained from peripheral blood or bone marrow
• Diagnosis of acute leukemia (acute myeloid leukemia \[AML\] or acute lymphoblastic leukemia \[ALL\]) in complete remission, or myelodysplastic syndrome (MDS)
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 from prior anti-cancer therapy
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 30 days prior to day 1 of protocol therapy)
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

You may not qualify if:

• Autologous stem cell transplant within 1 year prior to day 1 of protocol therapy
• Prior allogeneic transplantation
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy
• Note: Patients on maintenance chemotherapy with agents listed are not excluded
• Herbal medications
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• History of active tuberculosis
• Patients with history of thrombosis including but not limited to myocardial infarction (MI)/stroke and pulmonary embolism (PE)/deep vein thrombosis (DVT) within 6 months of enrollment
• Active diarrhea due to inflammatory bowel disease or malabsorption syndrome
• Clinically significant uncontrolled illness
• Active, uncontrolled systemic infection (viral, bacterial, or fungal) requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Other active malignancy
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Specimen Handling; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Methotrexate; merphos; ruxolitinib; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Haris Ali

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 13, 2023
• Study Start: July 16, 2024
• Primary Completion (Estimated): November 22, 2030
• Study Completion (Estimated): November 22, 2030
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (1)