Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia

NCT04994808 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1121616NCI-2021-0747410598
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trials studies the effect of treosulfan-based versus clofarabine-based conditioning regimens before donor hematopoietic stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Chemotherapy drugs, such as treosulfan, fludarabine, and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor hematopoietic stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. This study may help doctors determine whether treosulfan-based or clofarabine-based conditioning regimen works better before donor hematopoietic stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival

  At 6 months after transplant

Secondary Outcomes (5)

• Overall survival

  At 1 year after transplant

• Rate of non-relapse mortality

  At 1 year after transplant

• Relapse rate

  At 1 year after transplant

• Incidence of acute graft versus host disease

  At 1 year after transplant

• Duration of hospitalization

  Up to day 100 post hematopoietic stem cell transplantation

Study Arms (2)

Arm A (treosulfan, fludarabine, TBI, HCT)

EXPERIMENTAL

Patients receive treosulfan IV over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2. Patients also undergo TBI followed by HCT on day 0. Patients undergo ECHO or MUGA and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.

Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Radiation: Total-Body Irradiation; Drug: Treosulfan; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Lumbar Puncture; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection

Arm B (clofarabine, TBI, HCT)

EXPERIMENTAL

Patients receive clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI followed by HCT on day 0. Patients undergo ECHO or MUGA and lumbar puncture pre-transplant and undergo bone marrow aspiration, bone marrow biopsy, and collection of blood samples at pre-transplant and post-transplant.

Drug: Clofarabine; Procedure: Hematopoietic Cell Transplantation; Radiation: Total-Body Irradiation; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Lumbar Puncture; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection

Interventions

Clofarabine DRUG

Given IV

Also known as: Clofarex, Clolar

Arm B (clofarabine, TBI, HCT)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Arm A (treosulfan, fludarabine, TBI, HCT)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Infusion, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Treosulfan DRUG

Given IV

Also known as: 1,2,3, 4-Butanetetrol, 1,4-dimethanesulfonate, [R-(R*,S*)]-, Dihydroxybusulfan, Ovastat, Trecondi, Treosulphan, Tresulfon, Grafapex

Arm A (treosulfan, fludarabine, TBI, HCT)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: MUGA, MUGA Scan, Multi-Gated Acquisition Scan

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, spinal tap

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection

Arm A (treosulfan, fludarabine, TBI, HCT); Arm B (clofarabine, TBI, HCT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years and =\< 75 years
• Diagnosis of MDS-EB or AML: must have \< 5% marrow blasts (by morphology and/or flow cytometry) at time of transplant
• Karnofsky performance score (KPS) \>= 60% on pre-HCT evaluation
• Able to give informed consent
• Patients with previous autologous or allogeneic HCT may enroll
• DONOR: Human leukocyte antigen (HLA)-identical related donors or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for only one HLA allele at class I is allowed
• DONOR: Donors able to undergo peripheral blood stem cell collection. Only granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) will be permitted as an hematopoietic stem cell (HSC) source on this protocol

You may not qualify if:

• Presence of circulating blasts (in the blood) detected by standard pathology for patients with AML
• Presence of \>= 5% circulating leukemic blasts (in the blood) detected by standard pathology for patients with MDS-EB
• Patients with promyelocytic AML
• Organ dysfunction
• Cardiac: Ejection fraction \< 35% (or, if unable to obtain ejection fraction, shortening fraction of \< 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist
• Pulmonary:
• Diffusion capacity of the lung for carbon monoxide (DLCO) \< 40%, total lung capacity (TLC) \< 40%, forced expiratory volume in 1 second (FEV1) \< 40% and/or receiving supplementary continuous oxygen. When pulmonary function test (PFT)s cannot be obtained, the 6-minute walk test (6 minute walk functional test \[6MWT\], also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \< 89% during a 6MWT will be excluded
• The principal investigator (PI) must approve enrollment of all patients with pulmonary nodules
• Renal: Serum creatinine should be within normal limits as specified by Standard Practice guidelines. For subjects with serum creatinine \> upper limit of normal, a 24-hour creatinine clearance will be performed and should be equal to or more than the lower limit of normal
• Hepatic: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, or symptomatic biliary disease
• With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
• With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
• With central nervous system (CNS) leukemia at the time of treatment
• With life expectancy severely limited by diseases other than malignancy

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Medexus Pharma, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Clofarabine; fludarabine; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Whole-Body Irradiation; treosulfan; Spinal Puncture

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures

Study Officials

• Phuong Vo

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 6, 2021
• Study Start: August 11, 2023
• Primary Completion: January 22, 2026
• Study Completion (Estimated): July 16, 2026
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)