Melphalan and Radiation Therapy Followed By Lenalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Stage I, Stage II, or Stage III Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT00112827|
Recruitment Status : Active, not recruiting
First Posted : June 3, 2005
Last Update Posted : November 21, 2017
RATIONALE: Melphalan, a chemotherapeutic agent, has been found to be an effective treatment choice for destroying myeloma cells, especially when given at high (bone marrow ablative) doses. Total marrow irradiation (TMI)/ablative dose radiation therapy is another modality capable of destroying myeloma cells. Autologous peripheral blood/stem cell transplant (ASCT) given after either melphalan or following TMI (aimed at the bone marrow containing areas of the skeleton, the site of origin of myeloma cells) will shorten the duration/alleviate the severity of both melphalan and marrow irradiation-associated side effects. Lenalidomide, an effective agent on its own right for the treatment of myeloma, has been shown to further enhance the beneficial effects of autologous stem cell transplants when given as maintenance therapy.
PURPOSE: This previously phase I trial established the maximum tolerated dose of TMI at 1600 cGy. The phase II part of this study is ongoing and is studying the effects of high-dose melphalan and ASCT, followed by TMI and a second ASCT, with subsequent maintenance lenalidomide. The study is conducted in patients with stages I-III myeloma, with specific emphasis on assessing complete and very good partial response rate conversions, progression-free and overall survival, and safety/feasibility of delivering the planned treatment regimen.
|Condition or disease||Intervention/treatment||Phase|
|Refractory Multiple Myeloma Smoldering Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma||Radiation: total marrow irradiation Drug: melphalan Procedure: peripheral blood stem cell transplantation Biological: filgrastim Genetic: fluorescence in situ hybridization Genetic: cytogenetic analysis Drug: cyclophosphamide Procedure: autologous-autologous tandem hematopoietic stem cell transplantation Drug: lenalidomide||Phase 1 Phase 2|
I. To assess the feasibility and toxicities of tandem cycle ablative therapy consisting first of high-dose melphalan and then escalating doses of fractionated total marrow irradiation (TMI) using helical tomotherapy in patients with advanced multiple myeloma.
II. To establish the maximum tolerated dose of TMI using helical tomotherapy. III. To assess response rate, progression free and over-all survival following treatment with tandem cycle ablative therapy consisting first of high-dose melphalan and then escalating doses of TMI using helical tomotherapy with Dexamethasone/Thalidomide maintenance therapy in patients with advanced multiple myeloma.
IV. To assess the feasibility of adding decadron and thalidomide as maintenance following the second cycle of high-dose therapy.
I. To perform cytogenetic, gene rearrangement, and fluorescence in situ hybridization (FISH) studies on baseline and post-treatment bone marrow and blood specimens and correlate the presence/persistence of these features with treatment outcome.
II. To bank/develop cell lines developed for future investigations of tumor biology, and for potential assessment of efficacy of novel therapeutic agents.
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
PRIMING AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Patients also receive filgrastim IV or subcutaneously daily beginning 24 hours after the administration of cyclophosphamide and continuing until apheresis is complete. Patients undergo apheresis until an adequate number of peripheral blood stem cells are collected.
Course 1: Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1. Patients then undergo autologous PBSC transplantation on day 0 and receive filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts recover.
Course 2: Beginning 6-18 weeks later, patients undergo TMI once or twice daily on days -4 to -1. Patients then undergo autologous peripheral blood stem cell transplant and receive filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts recover.
MAINTENANCE THERAPY: Beginning within 6-8 weeks of day 0 of course 2 (TMI), patients receive oral lenalidomide daily. Courses repeat every 28 days for approximately 3 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days, every 6 months for 1 year, and then annually for at least 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial|
|Actual Study Start Date :||November 2004|
|Estimated Primary Completion Date :||November 2018|
|Estimated Study Completion Date :||November 2018|
U.S. FDA Resources
Experimental: Arm I
See Detailed Description
Radiation: total marrow irradiation
Undergo irradiationDrug: melphalan
Other Names:Procedure: peripheral blood stem cell transplantation
Other Names:Biological: filgrastim
Other Names:Genetic: fluorescence in situ hybridization
Other Name: fluorescence in situ hybridization (FISH)Genetic: cytogenetic analysis
Correlative studiesDrug: cyclophosphamide
Other Names:Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Undergo transplantationDrug: lenalidomide
- Feasibility [ Time Frame: At 3 years ]
- Response rate [ Time Frame: At 3 years ]
- Progression-free survival [ Time Frame: At 3 years ]
- Overall survival [ Time Frame: At 3 years ]
- Assessment of cell biology [ Time Frame: At 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00112827
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||George Somlo||City of Hope Medical Center|