Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis
Condition: Anemia; ASXL1 Gene Mutation; EZH2 Gene Mutation; IDH1 Gene Mutation; IDH2 Gene Mutation; Plasma Cell Myeloma; Primary Myelofibrosis; Recurrent Plasma Cell Myeloma; Secondary Myelofibrosis; Thrombocytopenia
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thrombocytopenia; Primary Myelofibrosis
Intervention: Busulfan; Cyclophosphamide; Fludarabine; Hematopoietic Cell Transplantation; Laboratory Biomarker Analysis
Intervention description: Given IV; Given IV; Given IV; Undergo HSCT; Correlative studies
Intervention MeSH terms: Cyclophosphamide; Busulfan; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and
      cyclophosphamide in treating participants 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 participant they may help the participant'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 participants with multiple
      myeloma or myelofibrosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Participants must have one of the following diagnoses of multiple myeloma (MM) or
             primary/secondary myelofibrosis (MF)

          -  Participants must have histologically documented multiple myeloma (MM)

               -  Participants 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)

          -  Participants must have histologically documented myelofibrosis (MF)

               -  Participants with Dynamic International Prognostic Scoring System (DIPSS) plus
                  intermediate stage 2 or higher risk MF; OR

               -  Subset of intermediate stage 1 participants; 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 at one second (FEV1) or diffusion capacity of lung
             for carbon dioxide (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

          -  Participants 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