Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation in High Risk AML and Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT03121014|
Recruitment Status : Recruiting
First Posted : April 19, 2017
Last Update Posted : April 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Myelodysplastic Syndromes||Drug: Fludarabine Drug: Busulfan Drug: ATG Radiation: Total Marrow Irradiation Procedure: Stem Cell Product Infusion Drug: Tacrolimus Drug: Methotrexate||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation in High Risk AML and Myelodysplastic Syndromes|
|Actual Study Start Date :||April 24, 2017|
|Estimated Primary Completion Date :||April 24, 2023|
|Estimated Study Completion Date :||April 24, 2024|
Experimental: Patient Treatment
Patients will receive fludarabine 40 mg/m2 IVBP daily for day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800μM/min/ day from day -5 through day -2, and ATG (Thymoglobulin®) at 0.5 mg/kg IV on day -3, and 2 mg/kg on days -2 and day -1 (Only for recipients of stem cells from unrelated or mismatched donors). In addition to the above conditioning regimen all patients will receive TMI at a dose of 3Gy on days -3, -2 and -1. On day 0, the stem cell product will be infused according to BMT unit policy. Graft versus host disease (GVHD) prophylaxis will consist of administration of tacrolimus and methotrexate. Post-transplant evaluation will be done as per standard care with study data collected at day 30, 60, 90, 180, 365 and 2 years.
40 mg/m^2 IVBP daily for day -5 (5 days before stem cell infusion) through Day -2
Other Name: Fludara®
targeting a 4800μM/min/ day from day -5 through day -2
Other Name: Busulfex®
0.5 mg/kg IV on day -3, and 2 mg/kg on days -2 and day -1
Other Name: Thymoglobulin®
Radiation: Total Marrow Irradiation
dose of 3Gy on days -3, -2 and -1
Procedure: Stem Cell Product Infusion
Day 0 according to BMT unit policy
The starting dose is at 0.03 mg/kg/day IV continuous infusion over 24 hr from 4 PM on day -2. Dose will be adjusted to target trough levels of 5-15 ng/mL. More information is available in the protocol document.
Other Name: FK-506, Prograf®
10 mg/m^2 on Day 1, 8 mg/m^2 on Days 3, 6 and 11
Other Name: Trexall®
- Relapse free survival of approximately 30% in high-risk patients conditioned with the Fludarabine/ Busulfan regimen [ Time Frame: Up to 1 year ]Using a Simon 2 stage optimal design with α of 0.05 and power of 0.8, 15 patients will be enrolled in the first stage. If greater than 5 patients survive to 1 year without relapse the study will continue into stage 2. Recruitment will then continue to a total of 46 patients. In this expanded cohort, if a total of 18 or more patients survive to 1 year without relapse, the treatment will be judged efficacious and worthy of further study.
- Relapse free survival [ Time Frame: Up to 1 year ]It will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive at 1-year will also be estimated with a 90% exact binomial confidence interval.
- Overall survival [ Time Frame: Up to 1 year ]It will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive at 1-year will also be estimated with a 90% exact binomial confidence interval.
- Transplant related mortality rate [ Time Frame: Up to 1 year ]After accrual of 10 patients, analysis will be performed to ensure that the mortality rate does not exceed 30%. By calculation of confidence intervals to ensure the TRM not exceed 30%, accrual would be halted if n= 6 of 10 (lower bound of the exact, one-sided 90% CI is 35.4%).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121014
|Contact: Damiano Rondelli, MDfirstname.lastname@example.org|
|United States, Illinois|
|University of Illinois at Chicago||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Damiano Rondelli, MD 312-413-3547 email@example.com|
|Principal Investigator:||Damiano Rondelli, MD||University of Illinois at Chicago|