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 : September 6, 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%).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121014
|Contact: Damiano Rondelli, MDemail@example.com|
|United States, Illinois|
|University of Illinois at Chicago||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Damiano Rondelli, MD 312-413-3547 firstname.lastname@example.org|
|Principal Investigator:||Damiano Rondelli, MD||University of Illinois at Chicago|