Chemotherapy, Holmium Ho 166 DOTMP, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Holmium Ho 166 DOTMP may deliver radiation directly to cancer
      cells and cause less damage to normal tissue. Combining chemotherapy and holmium Ho 166 DOTMP
      with peripheral stem cell transplantation may allow the doctor to give higher doses of
      chemotherapy and holmium Ho 166 DOTMP and kill more tumor cells.

      PURPOSE: Phase I/II trial to study the effectiveness of combining holmium Ho 166 DOTMP with
      melphalan and peripheral stem cell transplantation in treating patients who have multiple
      myeloma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the radiation absorbed dose of holmium Ho 166 DOTMP to the kidney in patients
           with multiple myeloma, based on whole body gamma camera image data for comparison with
           that obtained using an ICRP mathematical model.

        -  Determine the average marrow dose of this drug in these patients using gamma camera
           whole body counts in patients receiving this drug.

        -  Determine the pharmacokinetics of this drug in these patients.

        -  Compare marrow dose estimates determined from gamma camera whole-body counts and thyroid
           uptake probe counts in patients receiving this drug.

        -  Evaluate intra-patient variability of the uptake of this drug in the bone with repeat
           tests.

        -  Determine whether the biodistribution and dosimetry is influenced by administering this
           drug as a bolus compared to a 15-minute infusion in these patients.

        -  Compare the reduction in dose rate from the 15-minute infusion vs the bolus injection of
           this drug to estimate the effect on kidney exposure in these patients.

        -  Determine the renal transit time for each patient after bolus injection of this drug and
           assess whether this information improves the dose estimate to kidney with the
           mathematical model.

        -  Determine whether there is correlation of renal transit time from technetium Tc
           99m-diethylenetriaminepentaacetic acid (DTPA) with holmium Ho 166 DOTMP.

        -  Determine the adverse events in patients receiving this drug.

        -  Determine the efficacy of a targeted therapy dose of holmium Ho 166 DOTMP with melphalan
           followed by autologous peripheral blood stem cell transplantation in these patients.

      OUTLINE: This is a multicenter study. Patients are entered into one of two cohorts.

        -  Cohort A: Patients receive a diagnostic dose of holmium Ho 166 DOTMP IV over 15 minutes
           on day 1 and then IV bolus on day 8.

        -  Cohort B: Patients receive a diagnostic dose of holmium Ho 166 DOTMP IV over 15 minutes
           on days 1 and 8.

      After each diagnostic dose, patients in both cohorts also undergo gamma camera imaging of the
      whole body on days 1 and 8.

      Approximately 1-3 weeks later, patients in both cohorts who demonstrate adequate uptake of
      the first diagnostic dose of holmium Ho 166 DOTMP into the bone marrow then receive
      therapeutic holmium Ho 166 DOTMP IV over 15 minutes once between days -13 to -10 followed by
      melphalan IV over 20-30 minutes once between days -10 to -1. Patients undergo autologous
      peripheral blood stem cell transplantation on day 0.

      Patients are followed monthly for 1 year and then every 3 months for 1 year.

      PROJECTED ACCRUAL: A minimum of 12 patients (6 per cohort) will be accrued for this study.
    

Intervention name(s): melphalan; peripheral blood stem cell transplantation; holmium Ho 166 DOTMP
Intervention type(s): Drug; Procedure; Radiation
Intervention MeSH terms: Melphalan
Primary purpose: Treatment
Keywords: refractory multiple myeloma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma