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Refractory Multiple MyelomaPhase 1/2NCT00112827

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

A Phase 1/2 study testing total marrow irradiation, melphalan and peripheral blood stem cell transplantation in people with Refractory Multiple Myeloma and Smoldering Multiple Myeloma, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 70 years
What is being tested?
total marrow irradiation, melphalan and peripheral blood stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
Nov 2004to 15 Feb 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

SECONDARY OBJECTIVES:

  1. 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.

ABLATIVE THERAPY:

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.

Being tested
total marrow irradiation, melphalan, peripheral blood stem cell transplantation, filgrastim, fluorescence in situ hybridization
Medical subject headings
Multiple Myeloma, Smoldering Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • total marrow irradiationRadiation

    Undergo irradiation

  • melphalanDrug

    Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard

    Given IV

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo transplantation

  • filgrastimBiological

    Also called G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF

    Given IV

  • fluorescence in situ hybridizationGenetic

    Also called fluorescence in situ hybridization (FISH)

    Correlative studies

  • cytogenetic analysisGenetic

    Correlative studies

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • autologous-autologous tandem hematopoietic stem cell transplantationProcedure or surgery

    Undergo transplantation

  • lenalidomideDrug

    Also called CC-5013, IMiD-1, Revlimid

    Given orally

Study groups in NCT00112827
Study groupRoleWhat they receive
Arm IExperimentalSee Detailed Description
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 8 weeks from start of treatment, up to 2 years

  2. 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%.

    Measured: Evaluated after each course until completion of treatment.

  3. Overall Survival

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2005 (estimated)
  2. Study startNov 2004
  3. Primary completion15 Feb 2019
  4. Study completion15 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00112827
Sponsor's protocol ID
04064
Other IDs
CDR0000428410
Status last verified
Jun 2025
First submitted
2 Jun 2005
Last updated
6 Jun 2025
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing total marrow irradiation, melphalan and peripheral blood stem cell transplantation in people with Refractory Multiple Myeloma and Smoldering Multiple Myeloma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 8 weeks from start of treatment, up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00112827.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2025.

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