Stem Cell Transplantation To Treat High Risk Multiple Myeloma With Reduced Toxicity Myeloablative Conditioning Regimen

Phase 2

Terminated

Interventions: Drug: Fludarabine/Busulfan x 4 days
Procedure: stem cell transplant

Brief Summary: Standard therapy for multiple myeloma (MM) usually includes an autologous bone marrow stem cell transplant - a procedure where the patient is treated with high dose chemotherapy and then their own (autologous) stem cells are transplanted back into their body. Patients with multiple myeloma and high risk genes, always relapse after an autologous transplant and often die within two years from the time of their transplant. A different type of transplant allogeneic) using donor cells, may work better for high-risk Multiple Myeloma, because the donor cells may help kill the lymphoid cancer cells.

This study will investigate if a matched donor stem cell transplant using a newer, reduced toxicity, chemotherapy (Flu-Bu4) is a feasible option for patients with high risk, Multiple Myeloma.

Recruitment & Eligibility

Inclusion Criteria

Biologic high risk Multiple Myeloma:
- Stage II/III Multiple Myeloma, any of: t(4; 14), t(14; 16),(14:20) by Fish; 17P- by conventional cytogenetics or Fish; ∆13 by conventional cytogenetics; Hypodiploidy by conventional cytogenetics.
  - Relapsed or persistent multiple myeloma after ASCT.
  - Persistent multiple myeloma, regardless of previous therapies.
  - Plasma cell leukemia, regardless of previous therapies.
Age up to 70 years old (less than 71 years old at the date of transplant admission).
Disease status: in CR, nCR, VGPR, PR or stable disease within 1 month of admission
Patients with non-secretory and oligosecretory disease are eligible if they meet certain criteria within 2 weeks prior to the transplant.
Specific renal, liver, cardiac, and pulmonary function requirements(all must be met within 30 days of transplant admission)

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Flu-Bu4	Fludarabine/Busulfan x 4 days	Fludarabine Busulfan chemotherapy regimen(Flu-Bu4), followed by allogeneic stem cell transplant from best available, matched donor.
Flu-Bu4	stem cell transplant	Fludarabine Busulfan chemotherapy regimen(Flu-Bu4), followed by allogeneic stem cell transplant from best available, matched donor.

Primary Outcome Measures

Name	Time	Method
The Percentage of Patients Alive 1 Year Post Transplant	1 Year	The primary objective is overall survival, one year from the time of transplant.

Secondary Outcome Measures

Name	Time	Method
The Percentage of Patients Free From Progression at 1 Year	1 Year	One of the secondary outcomes that will be measured is progression free survival at 1 Year. Progressive Disease (PD) is defined as a \>25% increase in serum monoclonal paraprotein, a \>25% increase in 24-hour urinary light chain excretion, a \>25% increase in plasma cells in bone marrow aspirate, an increase in the size or the development of new bone lesions/soft tissue plasmacytomas, or the development of hypercalcemia.
Percentage of Patients With Treatment Related Mortality (TRM)	100 days, one-year
Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD)	100 days, 2 years	Incidence of acute (Stage II-IV and Stage III-IV) and chronic GVHD (any stage) were analyzed. Acute GVHD Grading: Stage II - Skin, 25-50% BSA (Body Surface Area); Liver, 3.1-6mg/dl bilirubin; Gut, 1000-1500ml/day diarrhea Stage III - Skin, generalized erythroderma; Liver, 6.1-15mg/dl bilirubin; Gut, \>1500ml/day diarrhea Stage IV - Skin, bullae; Liver, \>15mg/dl bilirubin; Gut, pain +/- ileus
Non Relapse Mortality (NRM) at 1 Year and 3 yearsThe Percentage of Deaths Not Attributable to Disease Relapse or Progression	3 years	Non relapse mortality, defined as the percentage of deaths not attributable to disease relapse or progression at 1 year and at 3 years.