Patient case: 50-year-old male with prostate cancer; genetic feature: ATM deletion

Clinical trial: Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Patients With Multiple Myeloma or Myelofibrosis

Summary: This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and cyclophosphamide in treating patients with multiple myeloma or myelofibrosis. Drugs used in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, 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 stem 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. Giving busulfan and fludarabine before and cyclophosphamide after donor stem cell may work better in treating patients with multiple myeloma or myelofibrosis.

Detailed description: PRIMARY OBJECTIVES:
  I. To evaluate non-relapse mortality (NRM) up to day +100.
  SECONDARY OBJECTIVES:
  I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.
  III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate clinical response and molecular response (complete response and partial response) up to 1 year.
  OUTLINE:
  Patients receive busulfan intravenously (IV) over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Patients undergo hematopoietic cell transplantation (HSCT) on day 0. Patients then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
  After completion of study treatment, patients are followed up for 1 year.

Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  -  Patients must have one of the following diagnoses of multiple myeloma (MM) or primary/secondary myelofibrosis (MF)
  -  Patients must have histologically documented multiple myeloma (MM)
  -  Patients in early relapse (less than 24 months from initiation of systemic anti-myeloma therapy which may include single or planned tandem autologous transplant) after primary therapy that included and autologous HSCT; OR
  -  Later stage; OR
  -  High risk factors defined by the presence of any one of the following detected at any time prior to enrollment: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1 (1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling; OR
  -  Extramedullary disease, plasma cell leukemia or high lactate dehydrogenase (LDH)
  -  Patients must have histologically documented myelofibrosis (MF)
  -  Patients with Dynamic International Prognostic Scoring System (DIPSS) plus intermediate stage 2 or higher risk MF; OR
  -  Subset of intermediate stage 1 patients; defined by:
  -  Poor-risk molecular profile (triple negative: JAK2, CALR, MPL); OR
  -  Presence of any of the following mutations: ASXL1, SRSF2, EZH2, IDH1/2; OR
  -  Severe thrombocytopenia, severe anemia, high peripheral blood blasts percentage; OR
  -  Unfavorable cytogenetic abnormalities (rearrangements of chromosome 5 or 7 or >= 3 abnormalities
  -  Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
  -  DONOR: A related donor - fully matched
  -  DONOR: A related donor - haploidentical
  -  DONOR: An unrelated donor - fully matched
  -  DONOR: An unrelated donor -9/10 matched
  Exclusion Criteria:
  -  Cardiac-left ventricular ejection fraction < 40%, symptomatic coronary artery disease, or uncontrolled arrhythmias
  -  Pulmonary-forced expiratory volume FEV1 or DLCO < 40% or history of chronic use of supplemental oxygen. Temporary use of supplemental oxygen at the time of screening or registration is allowed if the investigator feels that the underlying cause of requiring oxygen is reversible by the time treatment begins.
  -  Renal-calculated or measured glomerular filtration rate (GFR) < 30 ml/min, dialysis-dependent, or history of renal transplant
  -  Hepatic-bilirubin > 2 X upper limit of normal (ULN)
  -  Alanine aminotransferase (ALT) > 2.5 X ULN or cirrhosis
  -  Patients with active or uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
  -  Pregnant women, nursing mothers or women of child-bearing potential who are unwilling to use medically accepted methods of contraception
  -  Male and female subjects not willing to agree to medically accepted methods of contraception

Relevance to patient case: not relevant