A Feasibility Study of "Early" Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory High-Grade Myeloid Neoplasms

University of Washington1 site in 1 country30 target enrollmentSeptember 22, 2016

Overview

Phase: Phase 2
Intervention: Cladribine
Conditions: Blasts 10 Percent or More of Bone Marrow Nucleated Cells
Sponsor: University of Washington
Enrollment: 30
Locations: 1
Primary Endpoint: Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This clinical trial studies how well early stem cell transplantation works in treating patients with high-grade myeloid neoplasms that has come back after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as filgrastim, cladribine, cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor peripheral blood cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Early stem cell transplantation may result in more successful treatment for patients with high-grade myeloid neoplasms.

Detailed Description

OUTLINE: 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. 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) starting on day -3. Sirolimus PO BID starting on day -3 will be given to patients who have matched unrelated donors or mismatched unrelated donors. Patients \>55 years or with significant co-morbidities will only receive melphalan IV on day -2 and will 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 with matched donors will receive mycophenolate mofetil PO three times daily (TID) on days 0-30, then twice a day (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 BID on days -3 to 150, with a taper until day 180. Patients with mismatched unrelated donors will receive mycophenolate mofetil PO TID on days 0-30, then BID until day 100, with a taper until day 150; cyclosporine PO BID on days -3 to 150, then taper until day 180; and sirolimus BID PO days -3 to 180, then a taper until day 365. After completion of study treatment, patients are followed up periodically.

Registry

clinicaltrials.gov

Start Date

September 22, 2016

End Date

July 1, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Washington

Responsible Party

Principal Investigator

Mary-Beth Percival

Assistant Professor, Division of Hematology

University of Washington

Eligibility Criteria

Inclusion Criteria

•INCLUSION CRITERIA (ENROLLMENT)
•Relapsed or refractory high-grade myeloid neoplasms, defined as having a blast count of \>= 10% blasts at initial diagnosis; examples include excess blasts (EB)-2, with \>= 10% blasts at initial diagnosis, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML-2); standard definitions of relapse will apply (i.e., characterized by \>= 5% abnormal blasts or blast equivalents as assessed by multiparameter flow cytometry or morphologic examination; peripheral blood blasts or blast equivalents; or extramedullary granulocytic sarcoma, per European LeukemiaNet \[ELN\] 2017 guidelines); bone marrow aspirate/biopsy will be accepted if performed outside University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC); determination of disease status should occur within 30 days of signing informed consent
•R/R high-grade myeloid neoplasm following intensive induction chemotherapy; relapsed high-grade myeloid neoplasm: patients will be classified as relapsed if they have \>= 5% blasts after being in a complete remission (CR) following treatment for high-grade myeloid neoplasm; refractory high-grade myeloid neoplasm: patients may be classified as refractory if they have received at least one prior cycle of induction chemotherapy, whether with cladribine cytarabine mitoxantrone (GCLAM) or another regimen
•\*\* Patients may have received up to two courses of intensive induction chemotherapy during initial treatment prior to enrollment on this protocol; for example, patients who have received two courses of granulocyte colony stimulating factor (G-CSF) GCLAM (or similar) chemotherapy, with most recent high-dose cytarabine-containing chemotherapy \> 6 months ago and CR lasting \> 6 months, will be eligible for this protocol; regimens "similar to GCLAM" would include cytarabine at doses of 1g/m\^2 for at least 5 doses; examples of regimens "similar to GCLAM" would be GCLA, fludarabine cytarabine granulocyte (FLAG), and FLAG-idarubicin (ida); however, patients who received more than two courses of GCLAM (or similar) chemotherapy, or patients who received two courses of GCLAM and had CR lasting \< 6 months, would not be eligible
•R/R high-grade myeloid neoplasm following less intensive induction chemotherapy. Patients who have received at least three cycles of treatment with a hypomethylating agent (HMA; such as azacitidine or decitabine) and still have \>= 10% blasts will be eligible for the study (they will be considered refractory); similarly, patients who have received three or more cycles of HMA therapy who have had a response (e.g., achieving CR with \< 5% blasts), but who then progress using standard definitions of relapse, will also be eligible (they will be considered relapsed)
•Potentially eligible for reduced intensity conditioning based on known organ function (formal organ function testing may occur after consent)
•Caregiver capable of providing post-HCT care
•Written informed consent
•INCLUSION CRITERIA (TRANSPLANT)
•Identified donor (see DONOR SELECTION below for further details)

Exclusion Criteria

•EXCLUSION CRITERIA (ENROLLMENT)
•Prior allogeneic HCT
•More than two prior courses of induction chemotherapy
•Relapse after minimal residual disease (MRD)-negative CR within 3 months of most recent GCLAM chemotherapy
•Low likelihood of being eligible for reduced intensity conditioning HCT based on known information
•Cardiac ejection fraction \< 40% or symptomatic coronary artery disease or uncontrolled arrhythmia, as assessed by multigated acquisition (MUGA) or transthoracic echocardiography (TTE) within previous 3 months and since the most recent anthracycline exposure
•Corrected diffusing capacity of the lungs for carbon monoxide (DLCOc) \< 40% or forced expiratory volume in 1 second (FEV1) \< 50%
•Estimated glomerular filtration rate (GFR) \< 40 ml/min
•Need for supplemental oxygen
•Direct bilirubin or alanine aminotransferase (ALT) \> 2 x upper limit of normal, unless these abnormalities are thought to be related to Gilbert's disease or leukemic infiltration of hepatic parenchyma

Time Frame: 6 months after early allogeneic HCT on study

Success will be defined as observing a 40% of higher 6-month relapse-free survival among patients who received early transplant on study.

Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant

Time Frame: Up to 60 days after start of chemotherapy

Success will be defined as enrollment of at least 30 patients with transplants occurring in 15 of these 30 (50%) within 60 days of enrollment or start of induction chemotherapy with G-CLAM, whichever is earlier.

Secondary Outcomes

Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant(Up to 6 months after induction day 1)
Relapse-free Survival (RFS) Among Patients Who Received Early Transplant(Up to 6 months post-transplant)
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER(From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study))
Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants(Up to 12 months post-HCT)
Demonstrate the Feasibility of Collecting Resource Utilization Data for Trial Participants(Within the first year of induction chemotherapy on study)
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28(Approximately 28 days after early allogeneic HCT)
Acute Graft Versus Host Disease Among Patients Who Received Early Transplant(At day 100)
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84(Approximately 84 days after early allogeneic HCT)
Event-free Survival (EFS) Among Patients Who Received Early Transplant(Up to 6 months post-transplant)
Overall Survival (OS) Among Patients Who Received Early Transplant.(Up to 6 months post-transplant)
Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant(At day 100)
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY(From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study))
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE(From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study))