COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00112827
Recruitment Status : Completed
First Posted : June 3, 2005
Last Update Posted : November 20, 2019
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:

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

Detailed Description:


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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Primary Completion Date : February 15, 2019
Actual Study Completion Date : February 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm I
See Detailed Description
Radiation: total marrow irradiation
Undergo irradiation

Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan

Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

Biological: filgrastim
Given IV
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)

Genetic: cytogenetic analysis
Correlative studies

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Undergo transplantation

Drug: lenalidomide
Given orally
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid

Primary Outcome Measures :
  1. Feasibility [ Time Frame: At 3 years ]
  2. Response rate [ Time Frame: At 3 years ]
  3. Progression-free survival [ Time Frame: At 3 years ]
  4. Overall survival [ Time Frame: At 3 years ]

Secondary Outcome Measures :
  1. Assessment of cell biology [ Time Frame: At 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Patients with multiple myeloma (stages I-III) will be eligible if they are either in response, or have stable disease
  • Patients with smoldering myeloma are eligible if there is evidence of progressive disease requiring therapy (>= 25% increase in M protein levels or Bence Jones excretion; Hgb =< 10.5 g/dl; frequent infections; hypercalcemia; rise in serum creatinine above normal on two separate occasion)
  • Patients with non-quantifiable monoclonal proteins are eligible provided they meet other criteria for multiple myeloma, or smoldering myeloma, and they have evaluable or measurable disease by other (radiographic) means
  • Unlimited prior chemotherapy regimens allowed
  • KPS >= 70%
  • Patients with Waldenstrom's macroglobulinemia are not eligible
  • Less than 18 months since diagnosis
  • No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by apheresis
  • All patients must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
  • Adequate hepatic function as demonstrated by bilirubin, =< 1.5 mg/dl, and SGOT and SGPT < 2.5 x upper limits of normal
  • Adequate renal function as demonstrated by: creatinine of measured or calculated creatinine clearance of > 50 cc/min
  • Absolute neutrophil count of > 1000/ul, platelet count of > 100,000/ul
  • Cardiac ejection fraction >= 50% by MUGA scan and/or by echocardiogram
  • Adequate pulmonary function as demonstrated by FEV1 > 60% and DLCO > 50% of predicted lower limit
  • Hepatitis B antigen, Hepatitis C RNA and HIV antibody tests negative
  • No other medical, or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen
  • Females of reproductive age not using adequate birth control measures/ or who are pregnant are not eligible
  • History of other malignancies within the last 3 years, as long as patients have remained in complete remission for at least 2 years, except for non-melanoma skin cancer and in situ carcinoma of the cervix
  • Patients should have finished their prior chemotherapy at least 14 days prior to cyclophosphamide priming, and should have received their last dose of thalidomide, dexamethasone, or bisphosphonate > 10 days prior to cyclophosphamide priming
  • Pre-treatment tests must have been performed within 6 weeks prior to initiation of cyclophosphamide; A CBC, platelet count and comprehensive chemistry panel should be performed within 1 week prior to initiating cyclophosphamide priming
  • Known hypersensitivity to Filgrastim or to E. coli derived proteins is an exclusion
  • Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session, is an exclusion
  • Previous radiation therapy to more than 20% of bone marrow containing areas, or to any area exceeding 2000 cGy, is an exclusion
  • Patients must be fully aware of the teratogenic potential of thalidomide and agree to fully comply with the mandated guidelines regarding contraception as stated in the informed consent and the patient warning document attached to the consent form
  • Women of childbearing potential must have a negative pregnancy test performed within 24 hours prior to beginning thalidomide, except for woman who have been postmenopausal for at least 2 years, or underwent hysterectomy
  • Use of effective means of contraceptive should be started at least 2 weeks prior to initiating thalidomide

Information from the National Library of Medicine

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 identifier (NCT number): NCT00112827

Layout table for location information
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Layout table for investigator information
Principal Investigator: George Somlo City of Hope Medical Center
Layout table for additonal information
Responsible Party: City of Hope Medical Center Identifier: NCT00112827    
Other Study ID Numbers: COH 04064
CDR0000428410 ( Other Identifier: NCI PDQ )
First Posted: June 3, 2005    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents