Melphalan, Total Marrow Irradiation, and Autologous Stem Cell Transplantation in Treating Patients With High-Risk Multiple Myeloma

2017-04-05 02:08:21 | BioPortfolio


This phase I/II trial studies the side effects and best dose of melphalan and total marrow irradiation and how well they work with autologous stem cell transplantation in treating patients with high-risk multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Total marrow irradiation is a type of radiation therapy and a form of total body irradiation that may deliver focused radiation to the major marrow sites where cancer cells reside. Giving chemotherapy and total-body irradiation before a peripheral autologous blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.



I. To assess the safety and determine dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) of melphalan and fractionated total marrow irradiation (TMI) as conditioning regimen for autologous stem cell transplantation (ASCT) in patients with high-risk or treatment-insensitive multiple myeloma (MM). (Phase I) II. Evaluate the safety of the regimen at each dose levy by assessing adverse events: type, frequency, severity, attribution, time course, duration.

III. Evaluate the safety of the regimen at each dose level by assessing complication including: infection, delayed engraftment and secondary malignancy.

IV. To assess complete response (CR) and minimal residual disease (MRD) rates at 100 days post ASCT in a phase II expanded cohort of patients treated at the MTD. (Phase II)


I. To assess the predictive value of high risk features inclusive of fluorescent in situ hybridization (FISH), lactate dehydrogenase (LDH), International Staging System (ISS) stage, gene expression profiling (GEP) for CR and minimal residual disease (MRD) for relapse free survival/progression free survival/overall survival (RFS/PFS/OS) after melphalan TMI (mel/TMI).

II. To assess MRD by positron emission tomography (PET), next generation sequencing (NGS), and flow cytometry after mel/TMI, prior to maintenance and correlation with PFS and OS.

III. To assess in a descriptive fashion PFS and OS following mel/TMI and ASCT. IV. Evaluate changes in fludeoxyglucose F-18 (FDG) PET pre and post TMI/melphalan.


I. Assessment of bone marrow residual damage. II. Assessment of immune recovery dynamics. III. To conduct genetic profiling of myeloma cells. IV. Multimodal imaging for non-invasive assessment of treatment effect on bone and marrow.

OUTLINE: This is a phase I, dose-escalation study of melphalan and TMI followed by a phase II study.

MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide intravenously (IV) over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim subcutaneously (SC) or IV. Patients also undergo apheresis over 4 hours on day 10.

CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5.

MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide orally (PO) daily.

Study Design


Plasma Cell Leukemia in Remission


Autologous Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Filgrastim, Laboratory Biomarker Analysis, Lenalidomide, Leukapheresis, Melphalan, Palifermin, Total Marrow Irradiation


City of Hope Medical Center
United States


Not yet recruiting


City of Hope Medical Center

Results (where available)

View Results


Published on BioPortfolio: 2017-04-05T02:08:21-0400

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Medical and Biotech [MESH] Definitions

Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.

The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.

The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.

Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).

The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.

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