NCT00003954

Brief 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

Trial Health

85
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 1999

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2002

Completed
1.4 years until next milestone

First Posted

Study publicly available on registry

April 15, 2004

Completed
Last Updated

February 6, 2020

Status Verified

May 1, 2019

Enrollment Period

3.8 years

First QC Date

November 1, 1999

Last Update Submit

February 4, 2020

Conditions

Refractory Multiple MyelomaStage I Multiple MyelomaStage II Multiple MyelomaStage III Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

  • 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.

    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

  • Decrease in the short-term transplant-related mortality

    Day 100 after allograft

  • Establish stable allogeneic engraftment (mixed or full donor chimerism)

    At day 56 after allografting

Secondary Outcomes (4)

  • Overall survival

    Up to 3 years

  • Relapse rate

    Up to 3 years

  • Response rate

    Up to 3 years

  • Ability to convert mixed to full donor chimerism with DLI

    Up to 3 years

Study Arms (1)

Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)

EXPERIMENTAL

CONDITIONING 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.

Drug: melphalanProcedure: autologous hematopoietic stem cell transplantationProcedure: autologous bone marrow transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiationDrug: cyclosporineDrug: mycophenolate mofetilBiological: therapeutic allogeneic lymphocytes

Interventions

melphalanDRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
autologous hematopoietic stem cell transplantationPROCEDURE

Undergo autologous bone marrow or PBSCT

Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
autologous bone marrow transplantationPROCEDURE

Undergo autologous bone marrow or PBSCT

Also known as: ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
peripheral blood stem cell transplantationPROCEDURE

Undergo autologous bone marrow or PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
total-body irradiationRADIATION

Undergo TBI

Also known as: TBI
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
cyclosporineDRUG

Given IV and PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
mycophenolate mofetilDRUG

Given PO

Also known as: Cellcept, MMF
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
therapeutic allogeneic lymphocytesBIOLOGICAL

Undergo DLI

Also known as: ALLOLYMPH
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)

Eligibility Criteria

AgeUp to 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • 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)
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado

Denver, Colorado, 80217, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

University of Torino

Torino, 10126, Italy

Location

Related Publications (1)

  • 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.

    PMID: 32499241DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

MelphalanBone Marrow TransplantationTransplantationPeripheral Blood Stem Cell TransplantationWhole-Body IrradiationCyclosporineMycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsTissue TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsSurgical Procedures, OperativeHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationRadiotherapyInvestigative TechniquesCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipids

Study Officials

  • David Maloney

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 1999

First Posted

April 15, 2004

Study Start

March 1, 1999

Primary Completion

December 1, 2002

Last Updated

February 6, 2020

Record last verified: 2019-05

Locations

IT(1)US(3)