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

NCT ID: NCT05579769

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-14
• Study Completion Date: 2024-05-08

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

Conditions

Hematologic Malignancy; Myeloid Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplant Patients

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

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

Mesna

Intervention Type: 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.

Anti-thymocyte globulin (ATG)

Intervention Type: DRUG

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

Cyclosporine

Intervention Type: 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.

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: 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

Methotrexate

Intervention Type: DRUG

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

Total Body Irradiation (radiation treatment)

Intervention Type: 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.

Bone marrow infusion

Intervention Type: DRUG

Day 0

Busulfan

Intervention Type: DRUG

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

Thiotepa

Intervention Type: DRUG

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

Interventions

Ruxolitinib

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

Intervention Type: 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.

Intervention Type: DRUG

Anti-thymocyte globulin (ATG)

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

Intervention Type: 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.

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: 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

Intervention Type: DRUG

Methotrexate

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Bone marrow infusion

Day 0

Intervention Type: DRUG

Busulfan

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

Intervention Type: DRUG

Thiotepa

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

Intervention Type: DRUG

Other Intervention Names

(Jakafi®); (Mesnex); (Thymoglobulin®, rabbit ATG); (Gengraf); (Cytoxan); (Fludara); MTX; Amethopterin; TBI; Busulfex); Triplex by Immunex; TESPA; TSPA

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashok Srinivasan, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

CNI60

Identifier Type: -

Identifier Source: org_study_id