High-Dose Melphalan With or Without Radiolabeled Monoclonal Antibody in Treating Patients With Multiple Myeloma Undergoing an Autologous Stem Cell Transplant
- Conditions
- Multiple Myeloma and Plasma Cell Neoplasm
- Interventions
- Procedure: autologous hematopoietic stem cell transplantationRadiation: yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183
- Registration Number
- NCT00637767
- Lead Sponsor
- University of Southampton
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. A stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by the chemotherapy and radiolabeled monoclonal antibody.
PURPOSE: This randomized phase II trial is studying how well high-dose melphalan works when given with or without radiolabeled monoclonal antibody in treating patients with multiple myeloma undergoing an autologous stem cell transplant.
- Detailed Description
OBJECTIVES:
Primary
* To determine the efficacy of high-dose melphalan (200mg/m²) in combination with targeted radiotherapy delivered by yttrium Y 90 anti-CD66 monoclonal antibody BW250/183, in terms of disease response (complete remission rate and change in serum free light chain level before and after treatment with yttrium Y 90 anti-CD66 monoclonal antibody BW250/183), in patients undergoing autologous hematopoietic stem cell transplantation for multiple myeloma.
Secondary
* To determine the toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous hematopoietic stem cell transplantation.
* To determine the effect of targeted radiotherapy on other parameters of disease response, in terms of proportion of patients with partial remission, stable disease, and progressive disease, remission duration (time to disease progression), and overall survival.
* To determine the effect of targeted radiotherapy on engraftment when used in combination with high-dose melphalan in patients undergoing autologous hematopoietic stem cell transplantation for multiple myeloma.
* To investigate the pharmacokinetic behavior of indium In 111 anti-CD66 monoclonal antibody BW250/183 (used for dosimetry).
* To continue to develop a dosimetry model based on single-photon emission computed tomography (SPECT) and whole body gamma camera imaging following administration of the radiolabeled anti-CD66 monoclonal antibody (in a subset of patients at the Southampton site only).
* To assess the proportion of patients who form human anti-murine antibodies (HAMA) after treatment with targeted radiotherapy in the context of an autologous hematopoietic stem cell transplantation.
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk group (low risk \[beta-2 microglobulin and C-reactive protein \< 6 or either beta-2 microglobulin or C-reactive protein ≥ 6\] vs high risk \[both beta-2 microglobulin and C-reactive protein ≥ 6\]). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive a dosimetry dose of indium In 111 anti-CD66 monoclonal antibody BW250/183 IV on day 1 and undergo gamma camera imaging and serial blood samples on days 1-5. Patients then receive a therapeutic dose of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 IV once between days 9 and 16 and high-dose melphalan IV on day 28. Patients then undergo autologous hematopoietic stem cell transplantation (HSCT) on day 30.
* Arm II: Patients receive high-dose melphalan IV on day 1. Patients then undergo autologous HSCT on day 3.
Patients in arm I undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies and analysis of human anti-murine antibody (HAMA) status.
After completion of study treatment, patients are followed periodically.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description radio-labelled anti-CD66 monoclonal antibody autologous hematopoietic stem cell transplantation Up to 4mg radio-labelled anti-CD66 monoclonal antibody. Plus standard treatment radio-labelled anti-CD66 monoclonal antibody yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183 Up to 4mg radio-labelled anti-CD66 monoclonal antibody. Plus standard treatment No IMP - standard treatment autologous hematopoietic stem cell transplantation No IMP - standard treatment radio-labelled anti-CD66 monoclonal antibody melphalan Up to 4mg radio-labelled anti-CD66 monoclonal antibody. Plus standard treatment No IMP - standard treatment melphalan No IMP - standard treatment
- Primary Outcome Measures
Name Time Method Remission status pre- and post-transplantation, specifically the number of patients who achieve complete remission, as measured by the European Blood and Marrow Transplantation Organization Response Criteria end of study
- Secondary Outcome Measures
Name Time Method Disease response, as measured by changes in serum free light chains (in those patients with serum free light chains that are informative) end of study Pharmacokinetics of indium In 111 anti-CD66 monoclonal antibody BW250/183 as measured by serial blood samples and serial planar and single-photon emission computed tomography (SPECT) gamma camera imaging of selected organs end of study Treatment-related mortality end of study Engraftment quality, as measured by time to recovery of peripheral blood neutrophils to > 500/mm³ and platelets > 50, 000/mm³ and duration of recovery for > 180 days post-transplantation end of study Development of a dosimetry model based on SPECT and whole body gamma camera imaging end of study Proportion of patients who form human anti-murine antibodies (HAMA) after treatment with targeted radiotherapy in the context of an autologous hematopoietic stem cell transplantation end of study Disease response, including the proportion of patients with partial remission, stable disease, and progressive disease and remission duration (time to disease progression) end of study Overall survival end of study Toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous stem cell transplantation end of study
Trial Locations
- Locations (3)
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
🇬🇧Birmingham, England, United Kingdom
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom