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

NCT00112827 | Completed Phase 1 Results DMC

• 2 other identifiers: 04064CDR0000428410
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Multiple Myeloma; Smoldering Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  The highest dose tested (Total Marrow Irradiation) in which there is no treatment related mortality and none or only one patient experienced dose limited toxicity (DLT) attributable to the study drug(s), when at least six were fully treated at that dose and fully followed for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the treatment or there was a treatment related death. At least 6 patients will be treated at the MTD.

  8 weeks from start of treatment, up to 2 years

• Number of Subjects With Response

  Response defined as complete response or very good partial response. Complete response defined as the absence of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval. Thus all evidence of serum and urinary M-components must disappear on electrophoresis as well as by immunofixation studies. The follow-up bone marrow may not contain more than 5% plasma cells on aspiration or core biopsy and no evidence of increasing anemia. Skeletal X-rays must either show recalcification or no change in osteolytic lesions. Resolution of soft tissue plasmocytomas. Very good partial response defined as reduction of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval by greater than or equal to 90%.

  Evaluated after each course until completion of treatment.

• Overall Survival

  Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.

  From date of treatment until the date of death from any cause, assessed up to 14 years

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

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

Interventions

total marrow irradiation RADIATION

Undergo irradiation

Arm I

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, Melfalan

Arm I

peripheral blood stem cell transplantation PROCEDURE

Undergo transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Arm I

filgrastim BIOLOGICAL

Given IV

Also known as: G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Arm I

fluorescence in situ hybridization GENETIC

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Arm I

cytogenetic analysis GENETIC

Correlative studies

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Arm I

autologous-autologous tandem hematopoietic stem cell transplantation PROCEDURE

Undergo transplantation

Arm I

lenalidomide DRUG

Given orally

Also known as: CC-5013, IMiD-1, Revlimid

Arm I

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Criteria * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

Melphalan; Peripheral Blood Stem Cell Transplantation; Filgrastim; Granulocyte Colony-Stimulating Factor; In Situ Hybridization, Fluorescence; Cytogenetic Analysis; Cyclophosphamide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Genetic Techniques; Nucleic Acid Hybridization; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• George Somlo

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: November 1, 2004
• Primary Completion: February 15, 2019
• Study Completion: February 15, 2019
• Last Updated: June 6, 2025
• Results First Posted: March 1, 2021

Record last verified: 2025-06

Locations

US (1)