A Phase II Pediatric Study of a Graft-VS.-Host Disease (GVHD) Prophylaxis Regimen With no Calcineurin Inhibitors After Day +60 Post First Allogeneic Hematopoietic Cell Transplant for Hematological Malignancies

• Status: Not yet recruiting
• Trial end date: 2027-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The participants are being asked to take part in this clinical trial because the participant have a lymphoid or myeloid based cancer diagnosis that requires a bone marrow transplant.

Primary Objectives

To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies.

Secondary objective

Determine the cumulative incidence of relapse, NRM, chronic GVHD, and OS in study participants at one year post-transplant.

Exploratory objectives

• To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and rATG.

• To assess immune reconstitution in study participants within the first year post-HCT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Treatments: Antilymphocyte Serum; Busulfan; Cyclophosphamide; Cyclosporine; Cyclosporins; Fludarabine; Methotrexate; Thiotepa; Thymoglobulin

Criteria

Inclusion criteria

Diagnosis:

• Patients with high risk acute lymphoblastic leukemia in first remission. Examples include, but are not limited to, patients with certain leukemic cell cytogenetic findings (e.g. t(9;22) or t(4;11)); delayed response to induction chemotherapy; re-emergence of leukemic blasts by MRD (at any level) in patients previously MRD negative; persistently detectable MRD at lower levels; early T-cell precursor (ETP) ALL.

• Patients with acute lymphoblastic leukemia beyond first remission.

• Patients with Hodgkin's disease beyond first remission or with refractory disease.

• Patients with chronic myelogenous leukemia.

• Patients with primary or secondary myelodysplastic syndrome.

• Patients with Non-Hodgkin's lymphoma beyond first remission or with refractory disease.

• Patients with de novo acute myeloid leukemia in or beyond first remission or with relapsed or refractory disease, or myeloid sarcoma (extra-medullary AML).

• Patients with secondary acute myeloid leukemia.

• NK cell lymphoblastic leukemia in any CR.

• Biphenotypic, bilineage, or undifferentiated leukemia.

• Juvenile Myelomonocytic Leukemia (JMML)

• All patients with prior evidence of CNS leukemia must be treated and be in CNS CR.

Patients must have a related or unrelated donor matched at 12 of 12 HLA alleles.

Patient must have a Karnofsky/Lansky score of 70 or higher.

Patients must be 12 years of age or older.

Patients must have a shortening fraction >26% or left ventricular ejection fraction >40%.

Patients must have bilirubin less than or equal to 2.5 mg/dL and alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal.

Patients must have creatinine clearance, or a glomerular filtration rate (GFR), greater than 70 mL/min/1.73m2.

Patients must be free of severe infection that upon determination of principal investigator precludes BMT.

Patients must have FVC >50% predicted OR, if unable to perform pulmonary function testing, must maintain pulse oximetry oxygen saturation >92% on room air.

Female patients of childbearing age must have a negative pregnancy test.

Exclusion criteria

• Patients who have undergone prior HCT.

• Patients who have a peripheral blood stem cell graft source.

• Patients who have a non-permissive mismatch at the DPB1 allele.

• Patients who are HIV positive.

• Patients positive for Hepatitis B surface antigen (HBsAg).

• Patients positive for Hepatitis C.

• Patients with latent tuberculosis with positive TB IFN gamma release assay.