Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms
NCT ID: NCT02756572
Last Updated: 2021-11-08
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
30 participants
INTERVENTIONAL
2016-09-22
2020-07-01
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (chemotherapy, HCT)
See Detailed Description
Cladribine
Given IV
Cyclosporine
Given PO
Cytarabine
Given IV
Filgrastim
Given SC
Fludarabine Phosphate
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic stem cell transplantation
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Mitoxantrone Hydrochloride
Given IV
Mycophenolate Mofetil
Given PO
Questionnaire Administration
Ancillary studies
Sirolimus
Given PO
Total-Body Irradiation
Undergo TBI
Melphalan Hydrochloride
Given IV
Interventions
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Cladribine
Given IV
Cyclosporine
Given PO
Cytarabine
Given IV
Filgrastim
Given SC
Fludarabine Phosphate
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic stem cell transplantation
Laboratory Biomarker Analysis
Correlative studies
Melphalan
Given IV
Mitoxantrone Hydrochloride
Given IV
Mycophenolate Mofetil
Given PO
Questionnaire Administration
Ancillary studies
Sirolimus
Given PO
Total-Body Irradiation
Undergo TBI
Melphalan Hydrochloride
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* Identified donor (see DONOR SELECTION below for further details)
* Matched related or unrelated (one allele mismatch in HLA-A, B, or C OK) donor according to institutional standards
* Unrelated volunteer donor who is mismatched with the recipient (i.e. 9/10 match)
* Caregiver capable of providing post-HCT care, who will be present once induction therapy with filgrastim, cladribine, cytarabine, mitoxantrone hydrochloride (GCLAM) begins
* Written informed consent for transplant
* Either bone marrow or peripheral blood is allowed
Exclusion Criteria
* 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
* Known human immunodeficiency virus (HIV) positivity
* Pregnant or nursing (to be confirmed with quantitative human chorionic gonadotropin \[HCG\] testing)
* Invasive solid tumor within 5 years; non-melanoma skin cancer or in situ malignancies are allowed
* Evidence of serious uncontrolled infection
* Eastern Cooperative Oncology Group (ECOG) of 3 or 4
* Donor specific antibodies against donor HLA-DQ or -DP
* Active bacterial, fungal or viral infections unresponsive to medical therapy
* Active leukemia in the central nervous system (CNS)
* HIV positive
* Cardiac ejection fraction \< 40% or symptomatic coronary artery disease or uncontrolled arrhythmia
* DLCOc \< 40% or FEV1 \< 50%
* Estimated GFR \< 40 ml/min
* Need for supplemental oxygen
* Direct bilirubin or 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
DONOR SELECTION:
Identification of an appropriate donor will follow the general guidelines listed below.
* HLA-matched related or unrelated donor. Donors must be:
* Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
* Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
* HLA-mismatched unrelated donor. Unrelated volunteer donors who are mismatched with the recipient within one of the following limitations will be permitted:
* Mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele, but matched for HLA-DRB1 and HLA-DQ, OR
* Mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ
* HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch
HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQ. If the patient is homozygous at the mismatch HLA class I locus or II locus, the donor must be heterozygous at that locus and one allele must match the patient (i.e., patient is homozygous A\*01:01 and donor is heterozygous A\*01:01, A\*02:01)
18 Years
75 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
University of Washington
OTHER
Responsible Party
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Mary-Beth Percival
Assistant Professor, Division of Hematology
Principal Investigators
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Mary-Elizabeth Percival
Role: PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium
Locations
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Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2016-00477
Identifier Type: REGISTRY
Identifier Source: secondary_id
9567
Identifier Type: OTHER
Identifier Source: secondary_id
RG1016011
Identifier Type: OTHER
Identifier Source: secondary_id
9567
Identifier Type: -
Identifier Source: org_study_id