Using ruxolitinib, tacrolimus, and methotrexate to prevent graft versus host disease in young patients after bone marrow transplant
Phase 2a Study of Adding Ruxolitinib With Tacrolimus/Methotrexate Regimen for Graft-versus-Host Disease Prophylaxis in Myeloablative Conditioning Hematopoietic Cell Transplantation in Pediatric and Young Adult Patients
This study is testing if a combination of three medications can help prevent graft versus host disease in young patients after they receive a bone marrow transplant for certain types of leukemia or blood disorders.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 2 Years to 22 Years |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | Chemotherapy, immunotherapy, radiation, ruxolitinib, methotrexate |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT06128070 on ClinicalTrials.gov |
What this trial studies
This phase II trial evaluates the effectiveness and safety of combining ruxolitinib with tacrolimus and methotrexate to prevent graft versus host disease (GVHD) in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Ruxolitinib is a kinase inhibitor that blocks inflammatory signals, while tacrolimus and methotrexate are immunosuppressants that help reduce the risk of transplant rejection and GVHD. The study aims to assess the one-year rates of GVHD-free and relapse-free survival, along with secondary outcomes related to acute and chronic GVHD, overall survival, and complications post-transplant.
Who should consider this trial
Good fit: Ideal candidates are pediatric and young adult patients aged 2-22 with hematologic malignancies who are eligible for allogeneic bone marrow transplantation.
Not a fit: Patients who do not have a matched donor or those with severe comorbidities may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce the incidence of graft versus host disease in young patients undergoing bone marrow transplants.
How similar studies have performed: Other studies have explored similar combinations of immunosuppressants for GVHD prevention, showing promising results, but this specific combination is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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) Exclusion Criteria: * 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: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion. * 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 * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Haris Ali — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.