211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia
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|ClinicalTrials.gov Identifier: NCT03128034|
Recruitment Status : Recruiting
First Posted : April 25, 2017
Last Update Posted : August 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia in Remission High Risk Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome With Excess Blasts Recurrent Acute Myeloid Leukemia Refractory Acute Lymphoblastic Leukemia Recurrent Acute Lymphoblastic Leukemia Recurrent Mixed Phenotype Acute Leukemia Refractory Acute Myeloid Leukemia Refractory Mixed Phenotype Acute Leukemia||Drug: Cyclosporine Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Peripheral Blood Stem Cell Transplantation Other: Pharmacological Study Radiation: Pretargeted Radioimmunotherapy Drug: Sirolimus Radiation: Total-Body Irradiation Device: Fludarabine||Phase 1 Phase 2|
I. To estimate the maximum tolerated dose (MTD) of radiation delivered via 211^At-BC8-B10 when combined with fludarabine phosphate (FLU) and 2 or 3 gray (Gy) total body irradiation (TBI) as a preparative regimen for patients aged >= 18 with advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high risk myelodysplastic syndrome (MDS), or mixed-phenotype acute leukemia (MPAL).
I. To determine disease response and duration of remission. II. To determine the rates of engraftment and donor chimerism resulting from this combined preparative regimen, and to correlate level of donor chimerism with amount of 211^At administered.
OUTLINE: This is a dose-escalation study of 211^At-BC8-B10.
Patients receive 211^At-BC8-B10 intravenously (IV) over 6-8 hours on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and peripheral blood stem cell (PBSC) transplant on day 0. Patients also receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 56 and then tapered to day 180, or continuing to day 96 and then tapered to day 150. Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27, or every 8 hours on day 0 and then reduced to every 12 hours on days 30-40. Patients with HLA-matched unrelated donors receive sirolimus PO once daily (QD) on days -3 to 150 and then tapered to day 180.
After completion of study treatment, patients are followed up at 100 days and then at 6, 9, 12, 18 and 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study Evaluating Escalating Doses of 211^At-Labeled Anti-CD45 MAb BC8-B10 (211^At-BC8-B10) Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)|
|Actual Study Start Date :||October 24, 2017|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||March 22, 2023|
Experimental: Treatment (211^At-BC8-B10, PBSC)
Patients receive 211^At-BC8-B10 IV over 6-8 hours on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and PBSC transplant on day 0. Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 and then tapered to day 180, or continuing to day 96 and then tapered to day 150. Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27, or every 8 hours on day 0 and then reduced to every 12 hours on days 30-40. Patients with HLA-matched unrelated donors receive sirolimus PO QD on days -3 to 150 and then tapered to day 180.
Given PO or IV
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Given PO or IV
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSC transplant
Other: Pharmacological Study
Radiation: Pretargeted Radioimmunotherapy
Given 211^At-BC8-B10 IV
Radiation: Total-Body Irradiation
- Proportion of patients who develop grades III/IV Bearman regimen-related toxicity [ Time Frame: Up to 100 days following hematopoietic cell transplantation ]The maximum tolerated dose will be defined as the dose of 211^At-BC8-B10 used in combination with the reduced-intensity hematopoietic cell transplantation conditioning regimen that is associated with a grade III/IV regimen-related toxicity or true dose limiting toxicity rate of 25%.the data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited. Based on this fitted model, the maximum tolerated dose is estimated to be the dose that is associated with a toxicity rate of 25%.
- Achievement of remission [ Time Frame: Up to 2 years ]
- Disease-free survival [ Time Frame: Up to 100 days ]
- Duration of remission [ Time Frame: Up to 2 years ]
- Non-relapse mortality [ Time Frame: Up to 2 years ]
- Overall survival [ Time Frame: Up to 100 days ]
- Rates of acute graft versus host disease [ Time Frame: Up to day 180 ]
- Rates of chimerism [ Time Frame: Up to day 84 ]
- Rates of engraftment [ Time Frame: Up to day 100 ]Sufficient evidence will be taken to be a lower limit of the appropriate 80% one-sided confidence interval associated with the estimated proportion of rejections in excess of 0.20.
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): NCT03128034
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Brenda M. Sandmaier 206-667-4961 firstname.lastname@example.org|
|Principal Investigator: Brenda M. Sandmaier|
|Principal Investigator:||Brenda Sandmaier||Fred Hutch/University of Washington Cancer Consortium|