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

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

Interventions

DRUG

Ruxolitinib

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

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.

DRUG

Anti-thymocyte globulin (ATG)

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

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.

DRUG

Cyclophosphamide

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

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

DRUG

Methotrexate

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

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.

DRUG

Bone marrow infusion

Day 0

DRUG

Busulfan

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

DRUG

Thiotepa

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

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Ashok Srinivasan, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-03-14

Primary Completion

2024-05-08

Completion

2024-05-08

FDA Drug

Yes

Countries

• United States

Study Locations