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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase I-II Single Cycle Melphalan/Total Marrow Irradiation (TMI) and Autologous Stem Cell Transplantation (ASCT) Followed by Maintenance in Patients With High-Risk Myeloma and/or Poor Response to Indu

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

TER
Sponsor: City of Hope Medical Center

Current Primary Outcome:

  • Complete Response (CR) post-Autologous Stem Cell Transplantation (ASCT) (Phase II) [ Time Frame: Up to 3 years ]
    Will be summarized both by pooling across dose levels and by dose level.
  • Maximum Tolerated Dose (MTD) of mel/TMI (Phase I) [ Time Frame: Up to 3 years ]
    Toxicity information recorded will include the type, severity, and the probably association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.


Original Primary Outcome:

  • CR post-ASCT (Phase II) [ Time Frame: Up to 3 years ]
    Will be summarized both by pooling across dose levels and by dose level.
  • MTD of mel/TMI (Phase I) [ Time Frame: Up to 3 years ]
    Toxicity information recorded will include the type, severity, and the probably association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.


Current Secondary Outcome:

Original Secondary Outcome:

Information By: City of Hope Medical Center

Dates:
Date Received: March 29, 2017
Date Started: June 2017
Date Completion: June 2020
Last Updated: April 3, 2017
Last Verified: April 2017