Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
A Randomized Phase II Study of Treosulfan, Fludarabine and Low-Dose TBI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)
5 other identifiers
interventional
102
1 country
1
Brief Summary
This randomized phase II trial studies how well treosulfan and fludarabine phosphate, with or without total body irradiation before donor stem cell transplant works in treating patients with myelodysplastic syndrome or acute myeloid leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and mycophenolate mofetil after the transplant may stop this from happening.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2013
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2013
CompletedFirst Posted
Study publicly available on registry
July 10, 2013
CompletedStudy Start
First participant enrolled
November 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 9, 2017
CompletedResults Posted
Study results publicly available
May 21, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2022
CompletedJune 3, 2021
May 1, 2021
3.2 years
July 1, 2013
February 6, 2018
May 13, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants That Did Not Progress Within 6 Months
Progression is defined as relapse
At 6 months post-transplant
Secondary Outcomes (7)
Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Up to 84 days
Incidence of Chronic GVHD Graded by the NCI CTCAE Version 4.0
Up to 5 year
Incidence of Relapse/Progression
Up to 5 year
NRM
Up to 5 years
Overall Survival (OS)
Up to 2 year
- +2 more secondary outcomes
Study Arms (2)
Arm A
EXPERIMENTALArm A: Treosulfan, Fludarabine Phosphate Treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
Arm B
EXPERIMENTALArm B: Treosulfan, Fludarabine Phosphate, TBI Treosulfan and fludarabine phosphate as in Arm A and undergo low -dose total-body irradiation (TBI) on day 0
Interventions
Undergo allogeneic bone marrow transplant
Intravenously administered Fludarabine Phosphate
Undergo allogeneic PBSC transplant
Undergo TBI
Intravenously administered Treosulfan
Eligibility Criteria
You may qualify if:
- MDS, myelodysplastic syndrome/myeloproliferative neoplasia overlap disorders (including chronic myelomonocytic leukemia \[CMML\], and MDS/myeloproliferative neoplasm \[MPN\] unclassifiable syndromes)
- AML, other than acute promyelocytic leukemia (APL), in first or second remission or with minimal residual disease
- With Karnofsky index or Lansky Play-Performance scale \> 70% on pre-transplant evaluation
- Able to give informed consent (if \> 18 years), or with a legal guardian capable of giving informed consent (if \< 18 years)
- Patients with previous autologous or allogeneic HCT are allowed to enroll
- DONOR: Human leukocyte antigen (HLA)-identical related donors or
- DONOR: Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for one HLA allele is allowed
- DONOR: Donors able to undergo peripheral blood stem cell collection or bone marrow harvest
- DONOR: Donors in good general health, with a Karnofsky or Lansky play performance score \> 90%
- DONOR: Donors able to give informed consent (if \> 18 years), or with a legal guardian capable of giving informed consent (if \< 18 years)
You may not qualify if:
- Receiving umbilical cord blood
- With impaired cardiac function as evidenced by 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
- With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) \< 70 mm Hg and carbon monoxide diffusing capability test (DLCO) \< 70% of predicted or pO2 \< 80 mm Hg and DLCO \< 60% of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O2) saturation \< 92% on room air), or receiving supplementary continuous oxygen
- With impaired renal function as evidenced by creatinine-clearance \< 50% for age, weight, height or serum creatinine \> 2 x upper limit of normal or dialysis-dependent
- With hepatic dysfunction as evidenced by total bilirubin \> 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
- With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) \> 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
- With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
- With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis
- With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6)
- With life expectancy severely limited by diseases other than malignancy
- Women who are pregnant or lactating
- With known hypersensitivity to treosulfan or fludarabine (fludarabine phosphate)
- Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
- Unable to give informed consent (if \> 18 years) or with a legal guardian (if \< 18 years) unable to give informed consent
- DONOR: Individuals deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eileen J Sickle
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
H. Joachim Deeg
Fred Hutch/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 1, 2013
First Posted
July 10, 2013
Study Start
November 1, 2013
Primary Completion
January 9, 2017
Study Completion
June 1, 2022
Last Updated
June 3, 2021
Results First Posted
May 21, 2018
Record last verified: 2021-05