Clinical trial NCT05579769: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hematologic Malignancy
Myeloid Malignancy
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2022-10-14
Enrollment: 3
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The investigator propose to employ two preparative regimens based on the underlying hematological malignancy. For hematological malignancies of the lymphoid lineage we will use a standard preparative regimen consisting of Total Body Irradiation and cyclophosphamide (TBI/Cy), unless TBI is contraindicated. For myeloid malignancies we will use thiotepa, busulfan, and fludarabine (TBF), a preparative regimen that has been associated with a reduced risk of relapse and trend for improved survival with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy), our current regimen. All HCT recipients will receive cyclosporine in combination with methotrexate and ruxolitinib as GVHD prophylaxis. Recipients of MUD HCT will receive rATG for additional immunosuppression as is standard for unrelated donor transplants

Eligibility 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.

Primary outcomes:
measure: Proportion of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day 100 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies.
timeFrame: 100 days post transplant
Secondary outcomes:
measure: Incidence of Leukemic Relapse
timeFrame: One-year post-transplantation.
measure: Non-relapse mortality
timeFrame: One-year post-transplantation
measure: Overall Survival
timeFrame: one year post-transplantation
measure: Incidence of Chronic Graft Versus Host Disease (cGVHD)
timeFrame: 1 year post transplant
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Ashok Srinivasan, MD
role: PRINCIPAL_INVESTIGATOR
References: