Pediatric Study of GVHD Ppx w/o Calcineurin Inhibitors After Day60 Post First Allo HSCT for Hematological Malignancies.

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

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.

Study Overview

• Status: Terminated
• Conditions: Hematologic Malignancy; Myeloid Malignancy
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Mesna; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine; Drug: Cyclophosphamide; Drug: Methotrexate; Radiation: Total Body Irradiation (radiation treatment); Drug: Bone marrow infusion; Drug: Fludarabine; Drug: Busulfan; Drug: Thiotepa

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

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Transplant Patients

Drug: Ruxolitinib; Day +40 Dosage and Route of Administration-Ruxolitinib tablets should be administered orally BID, approximately every 12 hours, continuously, Oral; Other Names: (Jakafi®); Drug: Mesna; Days -3 and -2 Dosage and Route of Administration-Mesna is dosed based on the cyclophosphamide dose and generally administered in fractionated doses at approximately 20% of the total cyclophosphamide dose, Intravenous.; Other Names: (Mesnex); Drug: Anti-thymocyte globulin (ATG); Days -3, -2 and -1 Dosage and Route of Administration-(7 mg/kg total dose); intravenous.; Other Names: (Thymoglobulin®, rabbit ATG); Drug: Cyclosporine; Day -1 Dosage and Route of Administration-3 mg/kg; dose will be adjusted to maintain a steady concentration between 250-350 ng/mL or trough concentration between 175-250 ng/mL when transitioned to intermittent dosing.; Other Names: (Gengraf); Drug: Cyclophosphamide; Days -3 and -2 Dosage and Route of Administration-60 mg/kg for 2 consecutive days, (120 mg/kg total dose); intravenous.; Other Names: (Cytoxan); Drug: Methotrexate; Days +1, +3, +6 and +11 Dosage and Route of Administration-10 mg/m2/dose, intravenous; Other Names: MTX; Amethopterin; Radiation: Total Body Irradiation (radiation treatment); Days -7, -6, -5 and -4 6.2.3 Target Dose 1200 cGy total dose delivered 150 cGy per treatment fraction delivered BID over 4 days with 6 MV photons. Dose rate should be < 10 cGy/min in patients treated at extended SSD (450-500 cm) in the TBI couch and will be less than 15 cGy/min in young children and infants treated at extended SSD (200-220 cm) on the floor. Intra-fraction interval should be 6 hours. Custom posteriorly placed (PA only) partial transmission lung shields (blocks) will be used to reduce the average dose to the lung to approximately 1000 cGy total dose. An additional 400 cGy supplemental testicular radiation delivered in 2 fractions of 200 cGy delivered for males with lymphoid lineage leukemia.; Other Names: TBI; Drug: Bone marrow infusion; Day 0; Drug: Fludarabine; Days -4, -3 and -2 Dosage and Route of Administration-50 mg/m2 daily for 3 consecutive days (150 mg/m2 total dose) intravenous; Other Names: (Fludara); Drug: Busulfan; Days -4, -3 and -2 Dosage and Route of Administration-3.2 mg/kg/day; intravenous.; Other Names: Busulfex); Drug: Thiotepa; Days -6 and -5 Dosage and Route of Administration-(10 mg/kg total dose); intravenous; Other Names: TESPA; TSPA; Triplex by Immunex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of saGVHD Using a ProphylaxisRegimen With no Calcineurin Inhibitors After Day 100 Post First Allogeneic HLA-Matched Sibling or Unrelated Donor HCT for Hematological Malignancies.	Development of Severe Acute GVHD (saGVHD) at or before Day 100 post transplant is considered as an event. Severe acute GVHD is defined as grade II-IVGVHD. Acute graft-vs-host disease will be evaluated using the standard grading criteria.	100 days post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Overall Survival (OS)	The one-year survival is defined by the participant who has not died within one year after post transplantation. The rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.	One-year post-transplantation.
Cumulative Incidence of Relapse	Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.	One-year post-transplantation.
Cumulative Incidence of Non Relapse Mortality (NRM)	Non-relapse mortality is death without evidence of disease relapse or progression. The rate is calculated by computing the ratio between total number of NRM patients and the total number of patients.	One-year post-transplantation.
Cumulative Incidence of Chronic GVHD	Chronic graft-vs-host disease will be evaluated using the standard grading criteria.	One-year post-transplantation.

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Ashok Srinivasan, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): May 8, 2024
• Study Completion (Actual): May 8, 2024

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Therapeutics; Hydrocarbons, Acyclic; Hydrocarbons; Polycyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Alkanes; Alcohols; Butylene Glycols; Glycols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pterins; Pteridines; Aminopterin; Macrocyclic Compounds; Biological Products; Complex Mixtures; Triethylenephosphoramide; Aziridines; Azirines; Peptides, Cyclic; Sulfhydryl Compounds; Immune Sera; Methotrexate; Cyclophosphamide; Cyclosporine; Cyclosporins; Mesna; Busulfan; Thiotepa; Antilymphocyte Serum; Radiotherapy; fludarabine; fludarabine phosphate; ruxolitinib; Whole-Body Irradiation; thymoglobulin
• Other Study ID Numbers: CNI60

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
• IPD Sharing Time Frame: Data will be made available at the time of article publication.
• IPD Sharing Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes