Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms
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|ClinicalTrials.gov Identifier: NCT02756572|
Recruitment Status : Recruiting
First Posted : April 29, 2016
Last Update Posted : February 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Blasts 10 Percent or More of Bone Marrow Nucleated Cells Chronic Myelomonocytic Leukemia-2 High Grade Malignant Neoplasm Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts-2 Myeloid Neoplasm Previously Treated Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Cladribine Drug: Cyclosporine Drug: Cytarabine Biological: Filgrastim Drug: Fludarabine Phosphate Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Other: Laboratory Biomarker Analysis Drug: Melphalan Drug: Mitoxantrone Hydrochloride Drug: Mycophenolate Mofetil Other: Questionnaire Administration Drug: Sirolimus Radiation: Total-Body Irradiation Drug: Melphalan Hydrochloride||Not Applicable|
I. To evaluate the feasibility of "early" allogeneic hematopoietic cell transplant (HCT) for patients with relapsed or refractory (R/R) high-grade myeloid neoplasms.
I. Estimate relapse-free survival (RFS), acute graft versus host disease (GVHD), treatment related mortality (TRM), event-free survival (EFS), overall survival (OS), and complete remission (with or without measurable disease) among patients who receive early HCT.
II. Assess factors that distinguish patients who receive early HCT from those who do not.
III. Compare RFS, EFS, OS, acute GVHD, and TRM between patients in the feasibility study and matched patients who were transplanted with standard scheduling.
IV. Demonstrate the feasibility of collecting patient-reported outcomes and resource utilization data for trial participants.
V. Describe the outcomes of patients enrolled who went on to allogeneic HCT off-study.
RE-INDUCTION CHEMOTHERAPY: Patients receive filgrastim subcutaneously (SC) on days 0-5, mitoxantrone hydrochloride intravenously (IV) over 60 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and cytarabine IV over 2 hours on days 1-5. Treatment continues for a maximum of 2 courses in the absence of disease progression or unacceptable toxicity.
CONDITIONING REGIMEN: Beginning 14-60 days after re-induction chemotherapy, patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, melphalan IV on days -3 to -2, cyclosporine orally (PO) twice daily (BID) on day -3, and sirlolimus PO BID on day -3. Patients > 55 years or with significant co-morbidities also receive total body irradiation (TBI) on day -1 or day 0.
EARLY TRANSPLANT: Patients undergo allogeneic HCT after conditioning regimen on day 0.
GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil PO three times daily (TID) on days 0-30, then BID until day 40, and cyclosporine PO BID on days -3 to 96, with a taper until day 150. Patients with matched unrelated donors also receive sirolimus PO on days -3 to 150, with a taper until day 180.
After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Feasibility Study of "Early" Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory High-Grade Myeloid Neoplasms|
|Actual Study Start Date :||September 22, 2016|
|Estimated Primary Completion Date :||November 1, 2019|
Experimental: Treatment (chemotherapy, HCT)
See Detailed Description
Drug: Fludarabine Phosphate
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic stem cell transplantation
Other: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
Drug: Mycophenolate Mofetil
Other: Questionnaire Administration
Radiation: Total-Body Irradiation
Drug: Melphalan Hydrochloride
- Feasibility of early allogeneic hematopoietic cell transplant assessed by enrollment and incidence of early transplant [ Time Frame: Up to 60 days of start of chemotherapy ]Success will be defined as enrollment of at least 30 patients per year with transplants occurring in 15 of these 30 (50%) within 60 days of enrollment or start of induction chemotherapy, whichever is earlier.
- Event free survival [ Time Frame: Up to 12 months ]Will be estimated with the Kaplan-Meier method. Log-rank tests and Cox regression will be used for survival outcomes.
- Factors that distinguish patients who receive early hematopoietic cell transplant [ Time Frame: Up to 12 months ]Patients who receive early hematopoietic cell transplant will be compared to those that don't using Fisher's exact test for categorical variables (e.g., gender) and the Wilcoxon rank sum test for quantitative variables (e.g., age).
- Hematopoietic cell transplant Incidence of complete remission, defined as < 5% blasts on bone marrow biopsy with hematologic recovery, defined as absolute neutrophil count > 1000/ul and platelets > 100,000 /ml [ Time Frame: Up to 12 months ]
- Incidence of acute graft versus host disease (graft versus host disease graded II, III, or IV) [ Time Frame: At day 100 ]Cumulative incidence will be calculated and remission rates will be tabulated. Cumulative incidence regression will be used to compare outcomes subject to competing risks (acute graft versus host disease).
- Incidence of complete remission by platelets, defined as platelets < 100,000/ul [ Time Frame: Up to 12 months ]
- Incidence of complete remission with insufficient hematologic recovery, defined as absolute neutrophil count < 1000/ul or platelets < 100,000/ul [ Time Frame: Up to 12 months ]
- Incidence of relapse, defined as > 5% blasts in bone marrow, flow cytometry, or manual differential OR treatment for active relapsed disease [ Time Frame: Up to 12 months ]Prophylaxis against relapse or treatment for minimal residual disease (including donor lymphocyte infusion, genetically modified T cells or withdrawal of immunosuppression) will not be considered relapse for the purposes of this trial.
- Incidence of treatment related mortality [ Time Frame: At day 100 ]Cumulative incidence will be calculated and remission rates will be tabulated. Cumulative incidence regression will be used to compare outcomes subject to competing risks (treatment related mortality).
- Overall survival [ Time Frame: Up to 12 months ]Will be estimated with the Kaplan-Meier method. Log-rank tests and Cox regression will be used for survival outcomes.
- Patient-reported outcomes assessed by European quality of life five dimension [ Time Frame: Up to 12 months ]Results and resource utilization will be summarized descriptively and information gathering process will be assessed for feasibility.
- Patient-reported outcomes assessed by functional assessment cancer therapy-leukemia, and functional assessment cancer therapy-bone marrow transplant subscale [ Time Frame: Up to 12 months ]Results and resource utilization will be summarized descriptively and information gathering process will be assessed for feasibility.
- Patient-reported outcomes assessed by MD Anderson Symptom Inventory [ Time Frame: Up to 12 months ]Results and resource utilization will be summarized descriptively and information gathering process will be assessed for feasibility.
- Relapse free survival [ Time Frame: Up to 12 months ]Will be estimated with the Kaplan-Meier method. Log-rank tests and Cox regression will be used for survival outcomes.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02756572
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Mary-Elizabeth M. Percival 206-606-1320 firstname.lastname@example.org|
|Principal Investigator: Mary-Elizabeth M. Percival|
|Principal Investigator:||Mary-Elizabeth Percival||Fred Hutch/University of Washington Cancer Consortium|