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Refractory Multiple MyelomaPhase 1/2NCT00003954

Melphalan and Stem Cell Transplant Before Total-Body Irradiation and Donor Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma

A Phase 1/2 study testing melphalan, autologous hematopoietic stem cell transplantation and autologous bone marrow transplantation in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by Fred Hutchinson Cancer Center at 4 sites in 2 countries.

Completed

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

Official record
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Trial summary

In this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure Read more about this study

Who is it for?
Ages Up to 65 years
What is being tested?
melphalan, autologous hematopoietic stem cell transplantation and autologous bone marrow transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesin 2 countries
Study dates
Mar 1999to Dec 2002
Phase
Phase 1/2
Are there results?
None posted in the registry

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 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Meet Salmon and Durie criteria for initial diagnosis of multiple myeloma; transplant will be offered to patients with stage II or III multiple myeloma (MM) at diagnosis or have received chemotherapy and/or radiation therapy for progressive MM after initial diagnosis of stage I disease
  • The patient must have the capacity to give informed consent
  • Have received at least 4 cycles of conventional dose chemotherapy for MM
  • DONOR: HLA genotypically identical sibling
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for both peripheral blood stem cell (PBSC) allograft and subsequent DLI
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
  • DONOR: Age < 75, older donors may be considered after consultation by Psychological Consultation Center (PCC)

Who cannot join

  • Karnofsky score less than 60, unless due solely to myeloma
  • Left ventricular ejection fraction less than 40%
  • Bilirubin greater than 2 X the upper limit of normal
  • Serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 X the upper limit of normal
  • Diffusion lung capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen
  • Patients with poorly controlled hypertension
Show all 19Show fewer
  • Pregnancy
  • Seropositive for the human immunodeficiency virus
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Creatinine clearance < 40 cc/min at the time of initial autografting evaluation
  • Prior autograft (can be treated on alternative protocol)
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with human immunodeficiency virus (HIV)
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation as described in the standard practice guidelines of the institution

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • University of Colorado

    Denver, Colorado, 80217

  • City of Hope

    Duarte, California, 91010

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

Italy1 site

  • University of Torino

    Torino, 10126

Other trials in Italy

About this study

Official title: Allogeneic Stem Cell Transplantation For Multiple Myeloma: A Two Step Approach To Reduce Toxicity Involving High Dose Melphalan and Autologous Stem Cell Transplant Followed By PBSC Allografting After Low Dose TBI

In this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate engraftment of human leukocyte antigen (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200 cGy) and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in myeloma patients initially cytoreduced with high-dose melphalan.

II. To evaluate non-relapse mortality at day 100 post allografting. III. To evaluate the efficacy of this allografting strategy in terms of long-term progression free survival (PFS).

OUTLINE:

CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 15-20 minutes on day -2.

TRANSPLANTATION: Patients undergo autologous bone marrow or PBSC transplantation (PBSCT) on day 0.

NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV twice daily (BID) on days -1 and 0 and orally (PO) BID on days 1-80 with taper based on evaluation of disease response and graft-versus-host disease (GVHD). Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANTATION DONOR LYMPHOCYTE INFUSION (DLI): Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.

After completion of study treatment, patients are followed up for 3 years.

Being tested
melphalan, autologous hematopoietic stem cell transplantation, autologous bone marrow transplantation, peripheral blood stem cell transplantation, total-body irradiation
Medical subject headings
Multiple Myeloma

What participants receive

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

  • melphalanDrug

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

    Given IV

  • autologous hematopoietic stem cell transplantationProcedure or surgery

    Undergo autologous bone marrow or PBSCT

  • autologous bone marrow transplantationProcedure or surgery

    Also called ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow

    Undergo autologous bone marrow or PBSCT

  • peripheral blood stem cell transplantationProcedure or surgery

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

    Undergo autologous bone marrow or PBSCT

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • peripheral blood stem cell transplantationProcedure or surgery

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

    Undergo donor PBSCT

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given IV and PO

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO

  • therapeutic allogeneic lymphocytesBiological

    Also called ALLOLYMPH

    Undergo DLI

Study groups in NCT00003954
Study groupRoleWhat they receive
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)ExperimentalCONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2. TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0. NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27. POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
Receives: Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation; Drug: cyclosporine; Drug: mycophenolate mofetil; Biological: therapeutic allogeneic lymphocytes

What is being measured

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

  1. PFS

    The current study will be regarded as potentially efficacious if the observed 3-year PFS rate among all patients treated exceeds 30%. The Kaplan-Meier (KM) estimate of PFS will be used.

    Measured: From the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, up to 3 years

  2. Decrease in the short-term transplant-related mortality

    Measured: Day 100 after allograft

  3. Establish stable allogeneic engraftment (mixed or full donor chimerism)

    Measured: At day 56 after allografting

Secondary outcomes (4)

  1. Overall survival

    Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.

    Measured: Up to 3 years

  2. Relapse rate

    Summarized using cumulative incidence estimates. Confidence intervals will be estimated.

    Measured: Up to 3 years

  3. Response rate

    Confidence intervals will be estimated.

    Measured: Up to 3 years

  4. Ability to convert mixed to full donor chimerism with DLI

    Confidence intervals will be estimated.

    Measured: Up to 3 years

Timeline

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

  1. First posted15 Apr 2004 (estimated)
  2. Study startMar 1999
  3. Primary completionDec 2002

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
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003954
Sponsor's protocol ID
1383.00
Other IDs
NCI-2012-00670, P01CA078902
Status last verified
May 2019
First submitted
1 Nov 1999
Last updated
6 Feb 2020
Results posted
No

Publications

  • Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

    PubMed 32499241

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing melphalan, autologous hematopoietic stem cell transplantation and autologous bone marrow transplantation in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by Fred Hutchinson Cancer Center at 4 sites in 2 countries.

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

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. 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 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Italy. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

PFS (time frame: From the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, up to 3 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 NCT00003954, which also lists 1 linked publication.

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 Feb 2020.

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