Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)

Summary

This phase II trial tests whether treosulfan, fludarabine, and rabbit antithymocyte globulin (rATG) work when given before a blood or bone marrow transplant (conditioning regimen) to cause fewer complications for patients with bone marrow failure diseases. Chemotherapy drugs, such as treosulfan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Fludarabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. rATG is used to decrease the body's immune response and may improve bone marrow function and increase blood cell counts. Adding treosulfan to a conditioning regimen with fludarabine and rATG may result in patients having less severe complications after a blood or bone marrow transplant.

Conditions

• Bone Marrow Failure Syndrome
• Congenital Amegakaryocytic Thrombocytopenia
• Diamond-Blackfan Anemia
• Hereditary Sideroblastic Anemia
• Paroxysmal Nocturnal Hemoglobinuria
• Shwachman-Diamond Syndrome
• Hematologic Neoplasm With Germline GATA2 Mutation
• Hematologic Neoplasm With Germline SAMD9 Mutation
• Hematologic Neoplasm With Germline SAMD9L Mutation

Interventions

DRUG

Treosulfan

Given IV

DRUG

Fludarabine Phosphate

Given IV

DRUG

Tacrolimus

Given IV and PO

DRUG

Methotrexate

Given IV

BIOLOGICAL

Lapine T-Lymphocyte Immune Globulin

Given IV

PROCEDURE

Peripheral Blood Stem Cell Transplantation

Undergo PBSC

PROCEDURE

Allogeneic Bone Marrow Transplantation

Undergo bone marrow transplant

OTHER

Quality-of-Life Assessment

Ancillary studies

PROCEDURE

Echocardiography

Undergo ECHO

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

X-Ray Imaging

Undergo chest x-ray

PROCEDURE

Computed Tomography

Undergo chest CT

Sponsors & Collaborators

• Blood and Marrow Transplant Clinical Trials Network

  collaborator NETWORK

• National Cancer Institute (NCI)

  collaborator NIH

• National Marrow Donor Program

  collaborator OTHER

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Lauri Burroughs, MD · Fred Hutch/University of Washington Cancer Consortium

• Margaret MacMillan, MD · University of Minnesota

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

49 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-04-19

Primary Completion

2026-02-18

Completion

2026-02-18

FDA Drug

Yes

Countries

• United States

Study Locations