Conditioning Regimen of Bendamustine and Melphalan Followed by Transplant in Patients With Multiple Myeloma

• To determine the maximally tolerated dose of bendamustine in combination with melphalan as an autologous regimen based on dose limiting toxicities. [ Time Frame: 35 days post autologous stem cell transplant ] [ Designated as safety issue: Yes ]
• Survival, overall and progression free [ Time Frame: 100 days, 1 year, and overall after autologous stem cell transplant ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the safety and efficacy of Bendamustine (TREANDA™), in combination with Melphalan in subjects with multiple myeloma who are undergoing an Autologous Stem Cell Transplant.

Bendamustine (TREANDA™) has been used in clinical trials to treat multiple myeloma. The results from these trials suggest that it may be beneficial in the treatment of multiple myeloma in a different treatment context. Researchers aim to determine if there may be an improved benefit in the context of bone marrow transplant. This initial clinical trial is intended to help determine how safe it is to use bendamustine as a conditioning regimen for bone marrow transplant, and to look for any initial evidence of benefit.

Bendamustine (TREANDA™) is approved by the Food and Drug Administration (FDA) for the treatment of Chronic Lymphocytic Leukemia and Melphalan is a type of chemotherapy drug.

The use of Melphalan alone as a conditioning regimen for Autologous Stem Cell Transplant is considered "Standard of Care," that is, the treatment or process that your doctor would normally follow to treat your disease. Although Bendamustine (TREANDA™) has been used in multiple myeloma research studies, the combination of Bendamustine (TREANDA™) and Melphalan as treatment for Multiple Myeloma is not approved by the FDA, thus the combination therapy used in this research study is considered "investigational."

• Drug: Bendamustine
  30 mg/m2 given on day 2 of melphalan
  Other Name: Treanda
• Drug: Melphalan
  70 mg/m2 given 2 and 3 days prior to autologous cell transplant
  Other Name: Alkeran
• Drug: Bendamustine
  60 mg/m2 given on the 2nd day of melphalan
  Other Name: Treanda
• Drug: Bendamustine
  90 mg/m2 given on the 2nd day of melphalan
  Other Name: Treanda
• Drug: Bendamustine
  60 mg/m2 given on the 1st and 2nd day of melphalan
  Other Name: Treanda
• Drug: Bendamustine
  90 mg/m2 given on the 1st day of melphalan and 60 mg/m2 given on the 2nd day of melphalan
  Other Name: Treanda

• Experimental: 1
  Dose Level 1
  Interventions:

  • Drug: Bendamustine
  • Drug: Melphalan
• Experimental: 2
  Dose Level 2
  Interventions:

  • Drug: Melphalan
  • Drug: Bendamustine
• Experimental: 3
  Dose Level 3
  Interventions:

  • Drug: Melphalan
  • Drug: Bendamustine
• Experimental: 4
  Dose Level 4
  Interventions:

  • Drug: Melphalan
  • Drug: Bendamustine
• Experimental: 5
  Dose Level 5
  Interventions:

  • Drug: Melphalan
  • Drug: Bendamustine

Inclusion Criteria:

• Patients with multiple myeloma who have received induction therapy and have had stem cells mobilized in preparation for autologous transplantation will be eligible for this study. Patients are also eligible with relapsed or refractory disease, after attempts at more standard approaches, and with the availability of stem cells.
• Patients must be age 18 or older.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must have an ECOG performance status of 0, 1 or 2.
• Patients must provide written informed consent.

Exclusion Criteria:

• Impaired renal function with a measured or calculated creatinine clearance of less than 25 ml/min.
• Impaired hepatic function defined as a bilirubin greater than 1.5 x upper limit of normal (ULN) or ALT or AST greater than 5 x ULN.
• Serious active or uncontrolled infection or medical condition.
• Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.
• Impaired pulmonary function with a DLCO less than 45% predicted.
• Impaired cardiac function with an ejection fraction less than 40% of predicted.
• Other systemic anticancer therapy or ongoing toxicities from such therapy.