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

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.

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 sibling donor - fully matched

- DONOR: A sibling 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 in 1 second (FEV1) or carbon monoxide diffusing
capability (DLco) < 40% or need for use of supplemental oxygen

- Renal-calculated or measured glomerular filtration rate (GFR) < 40 ml/min, dialysis
requirement, or prior 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