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

NCT06008808 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202401211
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Haploidentical; GVHD; CRS

Outcome Measures

Primary Outcomes (3)

• Cumulative incidence of graft failure

  Day 35

• Cumulative incidence of grades III-IV acute GVHD by MAGIC criteria

  Day 100

• Number of patients who experience CRS

  Through day 14

Secondary Outcomes (3)

• Cumulative incidence of grades II-IV acute GVHD by MAGIC criteria

  Day 100

• Non-relapse mortality

  Day 180

• Feasibility of regimen

  From day -3 to day 30

Study Arms (2)

Regimen 1: Ruxolitinib

EXPERIMENTAL

-Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC ≥ 1.5 K/cumm, hemoglobin ≥ 9.0 g/dL, and platelets ≥ 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID.

Drug: Ruxolitinib

Regimen 2: Ruxolitinib + Abatacept

EXPERIMENTAL

* Ruxolitinib at 5 mg twice per day (BID) beginning on Day -3 and continuing until Day 180 followed by a taper (duration of taper depends on dose of ruxolitinib at Day 180). Once a patient's counts have reached ANC ≥ 1.5 K/cumm, hemoglobin ≥ 9.0 g/dL, and platelets ≥ 50 K/cumm, ruxolitinib dosing will escalate to 10 mg BID. * In addition, patients will receive abatacept 10 mg/kg IV over 30 minutes on days +5, +14, +28, and +56.

Drug: Ruxolitinib; Drug: Abatacept

Interventions

Ruxolitinib DRUG

Ruxolitinib is provided by Incyte Corporation.

Also known as: Jakafi

Regimen 1: Ruxolitinib; Regimen 2: Ruxolitinib + Abatacept

Abatacept DRUG

Abatacept is commercially available.

Regimen 2: Ruxolitinib + Abatacept

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria within 30 days prior to Day -3 unless otherwise noted.
• Diagnosis of one of the hematological malignancies listed below:
• 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).
• Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative by flow cytometry with sensitivity to ≤ 10-4).
• Myelodysplastic syndrome with ≤ 10% blasts in bone marrow.
• Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HD) in second or greater complete or partial remission.
• 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.
• AML in partial response. One patient will be enrolled in Regimen 1 given the prospect of potential benefit.
• Planned treatment is T cell-replete peripheral blood haploidentical donor transplantation.
• Available HLA-haploidentical donor who meets the following criteria:
• Blood-related family member, including (but not limited to) sibling, offspring, cousin, nephew, or parent. Younger donors should be prioritized.
• At least 18 years of age.
• HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards.
• In the investigator's opinion, is in general good health and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cells.
• No active hepatitis.

You may not qualify if:

• Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of ≥ 4000 as assessed by the single antigen bead assay.
• Known HIV or active hepatitis B or C infection. Known current history of active tuberculosis.
• Known hypersensitivity to one or more of the study agents.
• Planning to receive antithymocyte globulin as part of the pre-transplant conditioning regimen.
• Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -3).
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of Day -3.
• 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.
• Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Incyte Corporation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ruxolitinib; Abatacept

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Ramzi Abboud, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ramzi Abboud, M.D.

CONTACT

314-454-8304; rabboud@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 24, 2023
• Study Start: May 7, 2024
• Primary Completion (Estimated): September 8, 2027
• Study Completion (Estimated): November 27, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)