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

NCT05579769 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CNI60
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Malignancy; Myeloid Malignancy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Cumulative Incidence of Overall Survival (OS)

  One-year post-transplantation.

• Cumulative Incidence of Relapse

  One-year post-transplantation.

• Cumulative Incidence of Non Relapse Mortality (NRM)

  One-year post-transplantation.

• Cumulative Incidence of Chronic GVHD

  One-year post-transplantation.

Study Arms (1)

Transplant Patients

EXPERIMENTAL

Drug: Ruxolitinib; Drug: Mesna; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Methotrexate; Radiation: Total Body Irradiation (radiation treatment); Drug: Bone marrow infusion; Drug: Busulfan; Drug: Thiotepa

Interventions

Ruxolitinib DRUG

Day +40 Dosage and Route of Administration-Ruxolitinib tablets should be administered orally BID, approximately every 12 hours, continuously, Oral

Also known as: (Jakafi®)

Transplant Patients

Mesna DRUG

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.

Also known as: (Mesnex)

Transplant Patients

Anti-thymocyte globulin (ATG) DRUG

Days -3, -2 and -1 Dosage and Route of Administration-(7 mg/kg total dose); intravenous.

Also known as: (Thymoglobulin®, rabbit ATG)

Transplant Patients

Cyclosporine DRUG

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.

Also known as: (Gengraf)

Transplant Patients

Cyclophosphamide DRUG

Days -3 and -2 Dosage and Route of Administration-60 mg/kg for 2 consecutive days, (120 mg/kg total dose); intravenous.

Also known as: (Cytoxan)

Transplant Patients

Fludarabine DRUG

Days -4, -3 and -2 Dosage and Route of Administration-50 mg/m2 daily for 3 consecutive days (150 mg/m2 total dose) intravenous

Also known as: (Fludara)

Transplant Patients

Methotrexate DRUG

Days +1, +3, +6 and +11 Dosage and Route of Administration-10 mg/m2/dose, intravenous

Also known as: MTX, Amethopterin

Transplant Patients

Total Body Irradiation (radiation treatment) RADIATION

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.

Also known as: TBI

Transplant Patients

Bone marrow infusion DRUG

Day 0

Transplant Patients

Busulfan DRUG

Days -4, -3 and -2 Dosage and Route of Administration-3.2 mg/kg/day; intravenous.

Also known as: Busulfex)

Transplant Patients

Thiotepa DRUG

Days -6 and -5 Dosage and Route of Administration-(10 mg/kg total dose); intravenous

Also known as: Triplex by Immunex, TESPA, TSPA

Transplant Patients

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

ruxolitinib; Mesna; Antilymphocyte Serum; thymoglobulin; Cyclosporine; Cyclosporins; Cyclophosphamide; fludarabine; fludarabine phosphate; Methotrexate; Whole-Body Irradiation; Radiotherapy; Busulfan; Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Investigative Techniques; Butylene Glycols; Glycols; Alcohols; Mesylates; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Ashok Srinivasan
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

8662785833

Study Officials

• Ashok Srinivasan, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 14, 2022
• Study Start: March 14, 2023
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• 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.

Locations

US (1)