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RecruitingNCT04375631

CLAG-M or FLAG-Ida Chemotherapy and Reduced-Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelomonocytic Leukemia

CLAG-M or FLAG-Ida Chemotherapy Followed Immediately by Related/Unrelated Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1 Study

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
120 (estimated)
Sponsor
Fred Hutchinson Cancer Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial studies the best dose of total body irradiation when given with cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) or idarubicin, fludarabine, cytarabine and filgrastim (FLAG-Ida) chemotherapy reduced-intensity conditioning regimen before stem cell transplant in treating patients with acute myeloid leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Giving chemotherapy and total body irradiation before a donor peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can attack the body's normal cells called graft versus host disease. Giving cyclophosphamide, cyclosporine, and mycophenolate mofetil after the transplant may stop this from happening.

Detailed description

OUTLINE: This a dose-escalation study of TBI. Patients are assigned to 1 of 2 arms. ARM I: Patients receive filgrastim (G-CSF) subcutaneously (SC) daily on days -9 to -4, cladribine intravenously (IV) over 2 hours daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and mitoxantrone IV over 60 minutes daily on days -8 to -6. If white blood cell (WBC) \> 20,000/uL, filgrastim on days -9 and -8 may be omitted at physician discretion. Patients undergo TBI on either day -1 or 0 and HCT on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours daily on days 3-4, cyclosporine IV over 1-2 hours twice daily (BID) on days 5-60, and mycophenolate mofetil IV or orally (PO) BID on days 5-28 (transplant with related donors) or three times daily (TID) on days 5-35 (transplant with unrelated donors). After day 60, patients continue to receive cyclosporine tapered through day 180 at the discretion of the treating physician in the absence of GVHD. ARM II: Patients receive G-CSF SC daily on days -9 to -4, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and idarubicin IV over 60 minutes daily on days -8 to -6. If white blood cell (WBC) \> 20,000/uL, filgrastim on days -9 and -8 may be omitted at physician discretion. Patients undergo TBI on either day -1 or 0 and HCT on day 0. Patients receiving an unrelated cord blood (UCB) transplant also receive cyclophosphamide IV on day -2. GVHD PROPHYLAXIS: Patients who received peripheral blood stem cell transplant receive cyclophosphamide IV over 1-2 hours daily on days 3-4, cyclosporine IV over 1-2 hours BID on days 5-60, and mycophenolate mofetil IV or PO BID on days 5-28 (transplant with related donors) or TID on days 5-35 (transplant with unrelated donors). After day 60, patients continue to receive cyclosporine tapered through day 180 at the discretion of the treating physician in the absence of GVHD. Patients who received an UCB transplant receive cyclosporine IV, over 1 hour, every 8 hours (Q8H) from day -3 until day +100 and mycophenolate mofetil IV or PO TID on days 5-35. After day 100 patients continue to receive cyclosporine tapered up to at least 6 months post-transplant. Patients in both arms undergo multigated acquisition scan (MUGA) or echocardiography, and x-ray imaging during screening and as clinically indicated or per standard practice. Patients also undergo bone marrow biopsy and aspirate during screening, day 28, day 80 and at 1 year. Additionally, patients undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up at 100 days, at 6, 12, and 24 months post-transplant.

Conditions

Interventions

TypeNameDescription
DRUGCladribineGiven IV
DRUGCyclophosphamideGiven IV
DRUGCyclosporineGiven IV then PO
DRUGCytarabineGiven IV
BIOLOGICALFilgrastimGiven SC
PROCEDUREHematopoietic Cell TransplantationUndergo HCT
DRUGMitoxantroneGiven IV
DRUGMycophenolate MofetilGiven IV or PO
DRUGMycophenolate SodiumGiven PO
RADIATIONTotal-Body IrradiationUndergo TBI
DRUGIdarubicinGiven IV
DRUGFludarabineGiven IV
DRUGCytarabineGiven IV
PROCEDUREMultigated Acquisition ScanUndergo MUGA
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDUREX-Ray ImagingUndergo x-ray
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy and aspirate
PROCEDUREBone Marrow AspirationUndergo bone marrow biopsy and aspirate
PROCEDUREBiospecimen CollectionUndergo blood sample collection

Timeline

Start date
2020-12-03
Primary completion
2027-02-28
Completion
2027-03-17
First posted
2020-05-05
Last updated
2026-03-05

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04375631. Inclusion in this directory is not an endorsement.