RECRUITING

Ruxolitinib With and Without CTLA-4 Ig Abatacept for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation

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Conditions

Graft Vs Host DiseaseGraft-versus-host-diseaseGraft Versus Host DiseaseHaploidenticalGVHDCRS

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative intent therapies available for hematologic malignancies. HLA-matched sibling donors have historically offered the best clinical results but are unavailable for the majority of patients, while most patients do have readily available haploidentical donors. One of the risks of a haploidentical HCT is graft vs. host disease (GVHD), but it is difficult to reduce the incidence of GVHD without compromising the graft vs. leukemia (GVL) effect. The hypothesis of this study is that JAK inhibition with and without CTLA-4 Ig with haploidentical HCT may mitigate GVHD and cytokine release syndrome while retaining the GVL effect and improving engraftment.

Official Title

An Open-Label Phase I Study of JAK Inhibitor Ruxolitinib With and Without CTLA-4 Ig Abatacept for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation

Quick Facts

Study Start:2024-05-07
Study Completion:2026-12-11
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06008808

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Diagnosis of one of the hematological malignancies listed below:
  2. * Acute myelogenous leukemia (AML) in complete morphological remission, complete remission with incomplete hematologic recovery, and complete remission with partial hematologic recovery (based on ELN Criteria47).
  3. * Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative by flow cytometry with sensitivity to ≤ 10-4).
  4. * Myelodysplastic syndrome with ≤ 10% blasts in bone marrow.
  5. * Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HD) in second or greater complete or partial remission.
  6. * Myelofibrosis with ≤ 10% blasts in bone marrow. Up to five patients with myelofibrosis will be permitted in Regimen 1 and up to five in Regimen 2.
  7. * AML in partial response. One patient will be enrolled in Regimen 1 given the prospect of potential benefit.
  8. * Planned treatment is T cell-replete peripheral blood haploidentical donor transplantation.
  9. * Available HLA-haploidentical donor who meets the following criteria:
  10. * Blood-related family member, including (but not limited to) sibling, offspring, cousin, nephew, or parent. Younger donors should be prioritized.
  11. * At least 18 years of age.
  12. * HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards.
  13. * In the investigator's opinion, is in general good health and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cells.
  14. * No active hepatitis.
  15. * Negative for HTLV and HIV.
  16. * Not pregnant.
  17. * Donor selection will be in compliance with FDA guidelines as provided in 21 CFR 1271 for donor eligibility https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM091345.pdf
  18. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  19. * Adequate organ function as defined below:
  20. * Total bilirubin ≤ 1.5 x IULN.
  21. * AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.
  22. * Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 by Cockcroft-Gault Formula.
  23. * Oxygen saturation ≥ 90% on room air.
  24. * LVEF ≥ 40%.
  25. * FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is \< 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation.
  26. * Able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil (if applicable), and cyclophosphamide.
  27. * At least 18 years of age at the time of study consent
  28. * The effects of ruxolitinib and abatacept on the developing human fetus are unknown. Additionally, tacrolimus may increase risk of hypertension, preeclampsia, preterm birth, and low birth weight; and mycophenolate mofetil is considered to be teratogenic. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of the study.
  29. * Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  1. * Prior allogeneic transplant (regardless of whether donor was related, unrelated, or cord). Prior autologous transplant is not exclusionary.
  2. * Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of ≥ 4000 as assessed by the single antigen bead assay.
  3. * Known HIV or active hepatitis B or C infection. Known current history of active tuberculosis.
  4. * Known hypersensitivity to one or more of the study agents.
  5. * Planning to receive antithymocyte globulin as part of the pre-transplant conditioning regimen.
  6. * Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -3).
  7. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of Day -3.
  8. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, or unstable cardiac arrhythmias.
  9. * Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded.

Contacts and Locations

Study Contact

Ramzi Abboud, M.D.
CONTACT
314-454-8304
rabboud@wustl.edu

Principal Investigator

Ramzi Abboud, M.D.
PRINCIPAL_INVESTIGATOR
Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine
Saint Louis, Missouri, 63110
United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

  • Ramzi Abboud, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-07
Study Completion Date2026-12-11

Study Record Updates

Study Start Date2024-05-07
Study Completion Date2026-12-11

Terms related to this study

Keywords Provided by Researchers

  • Haploidentical
  • GVHD
  • CRS

Additional Relevant MeSH Terms

  • Graft Vs Host Disease
  • Graft-versus-host-disease
  • Graft Versus Host Disease