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

Overview

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.

Full Title of Study: “Allogeneic Hematopoietic Stem Cell Transplantation For The Treatment Of High Risk Multiple Myeloma With Reduced Toxicity Myeloablative Conditioning Regimen”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: December 2012

Interventions

• Drug: Fludarabine/Busulfan x 4 days
  • Fludarabine: 40 mg/m2/day in NS, administered IV over 30 minutes on days -5, -4, -3, and -2 pre-transplant. Busulfan: 3.2 mg/kg IV daily in NS over 4 hours on days -5, -4, -3, and -2. The Fludarabine shall be administered prior to the Busulfan each day.
• Procedure: stem cell transplant
  • Allogeneic, peripheral blood stem cell transplant

Arms, Groups and Cohorts

• Experimental: Flu-Bu4
  • Fludarabine Busulfan chemotherapy regimen(Flu-Bu4), followed by allogeneic stem cell transplant from best available, matched donor.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

• The Percentage of Patients Free From Progression at 1 Year
  • Time Frame: 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)
  • Time Frame: 100 days, one-year
• Percentage of Patients With Acute and Chronic Graft Versus Host Disease (GVHD)
  • Time Frame: 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
  • Time Frame: 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.

Participating in This Clinical Trial

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:

• Persistent invasive infections, not controlled by antimicrobials. – HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity. – Uncontrolled medical or psychiatric disorder. – No response or progressive disease at the time of transplantation. – Pregnancy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Michigan Rogel Cancer Center
• Collaborator
  • Otsuka Pharmaceutical Development & Commercialization, Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Attaphol Pawarode, MD, Principal Investigator, University of Michigan Dept. of Internal Medicine