Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Recurrence

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Leukemia, Myelomonocytic, Acute

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Disease Attributes

Bone Marrow Diseases

Precancerous Conditions

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Myeloid Leukemia

Acute Myeloid Leukemia

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Antirheumatic Agents

Dermatologic Agents

Cytarabine

Mitoxantrone

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

Cyclosporins

Lenograstim

Mycophenolic Acid

Idarubicin

Cladribine

2-chloro-3'-deoxyadenosine

2'-deoxyadenosine

Cordycepin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Antiviral Agents

Adjuvants, Immunologic

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Filgrastim

Hematopoietic Cell Transplantation

Mycophenolate Mofetil

Mycophenolate Sodium

Total-Body Irradiation

Multigated Acquisition Scan

Echocardiography

X-Ray Imaging

Bone Marrow Biopsy

Bone Marrow Aspiration

Filippo Milano

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.

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 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 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 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 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.

After completion of study treatment, patients are followed up at 100 days, at 6, 12, and 24 months post-transplant.

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

Defined as graft rejection (\< 5% donor T-cell chimerism).

Defined by European LeukemiaNet (ELN) 2017 criteria and International Working Group (IWG).

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for mycophenolate sodium