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Non-myeloablative Allogeneic Transplantation for the Treatment of 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.
 
ClinicalTrials.gov Identifier: NCT00185614
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : January 18, 2018
Last Update Posted : January 18, 2018
Sponsor:
Information provided by (Responsible Party):
Wen-Kai Weng, Stanford University

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 16, 2005
Results First Submitted Date  ICMJE October 31, 2017
Results First Posted Date  ICMJE January 18, 2018
Last Update Posted Date January 18, 2018
Study Start Date  ICMJE August 2000
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
Event-free Survival (EFS) [ Time Frame: 3 years ]
Event-free survival (EFS) as determined for all participants who received the initial Auto-HCT treatment. "Event" was defined as any of the following within 3 years of the participant's last infusion of Auto-HCT or Allo-HCT: relapse; death; or last follow-up if there is no data to document the participant remained alive at 3 years.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • Relapse Rate [ Time Frame: 3 years ]
    Relapse rate as determined for all participants who received the initial Auto-HCT treatment. Relapse was protocol-specified as progressive disease, indicated by an increase as compared to pre-Auto-HCT baseline, of serum or urine monoclonal protein >25%; bone marrow plasmacytosis >25%; or bone lesions on skeletal survey (any increase).
  • Overall Survival (OS) [ Time Frame: 3 years ]
    Overall Survival (OS) as determined for all participants who received the initial Auto-HCT treatment, as assessed from the date of the last transplant.
  • Acute Graft-vs-Host-Disease (aGvHD) [ Time Frame: 6 months ]
    Development of acute graft-vs-host-disease (aGvHD) within 6 months, for participants receiving Allo-HCT.
  • Chronic Graft-vs-Host-Disease (cGvHD) [ Time Frame: 3 years ]
    Development of chronic graft versus host disease (cGvHD) within 3 years, for participants receiving Allo-HCT. Reported as "Extensive cGvHD;" "cGvHD, Not Extensive;" or "No cGvHD," as determined by investigator judgement (no protocol-specified criteria).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Official Title  ICMJE Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Brief Summary Mixed chimerism transplantation is an approach to allogeneic transplants that attempts to decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish mixed chimerism using low dose total body irradiation along with immunosuppression using cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to convert the patient to a full chimera while developing a graft-vs-tumor effect.
Detailed Description Participants are mobilized with cyclophosphamide 4 g/m2 and filgrastim 10 µg/kg/day for peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue [ie, autologous hematopoietic cells transplant (auto-HCT)]. Post-infusion support includes filgrastim 5 µg/kg/day, starting 6 days following melphalan. Participants with stable or responsive disease at 4 weeks eligible to continue on to the planned allogenic HCT (allo-HCT). For allo-HCT, a sibling donor that is fully matched for human leukocyte antigen (HLA-matched) is identified. Participants receive a single dose of total body irradiation (TBI) 200 centigray (cGy) as well as immunosuppression with cyclosporine (CSP) 6.25 mg/kg and mycophenolate mofetil (MMF) 15 mg/kg. The HLA-matched donor begins filgrastim injections 16 µg/kg/day on day -4 continuing to Day 0, with apheresis collections on Day -1 and Day 0, to a target of > 5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication hydrocortisone 100 mg IV and diphenhydramine 50 mg IV. CSP will be tapered beginning Day 56 with a goal of discontinuing CSP on Day 180, adjusted as needed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Blood Cancer
  • Multiple Myeloma
Intervention  ICMJE
  • Procedure: Autologous hematopoietic cell transplant (Auto-HCT)
    The target cell dose is 2.6 x 10e6 CD34+ cells/kg
  • Procedure: Allogeneic hematopoietic cell transplant (Allo-HCT)
    The target cell dose is 5 x 10e6 CD34 cells/kg
  • Drug: Cyclophosphamide
    Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion
    Other Names:
    • Cytoxan
    • Neosar
  • Drug: Filgrastim
    • Filgrastim 10 µg/kg/day to mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion (Auto-HCT)
    • Filgrastim 5 µg/kg/day starting 6 days after melphalan (Day 4 after Auto-HCT)
    • Filgrastim 16 µg/kg/day to mobilize donor peripheral blood progenitor cells (PBPC) for allogeneic transplant (Allo-HCT)
    Other Names:
    • Neupogen
    • Granulocyte-colony stimulating factor (G-CSF)
  • Drug: Melphalan
    Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT
    Other Names:
    • Melphalan hydrochloride
    • Melphalan HCl
  • Radiation: Total body irradiation (TBI)
    200 centigray (cGy) total body irradiation delivered on Day 0
  • Procedure: Cyclosporine (CSP)
    Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56
    Other Name: Cyclosporine A
  • Drug: Mycophenolate Mofetil (MMF)
    Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27
    Other Name: CellCept
Study Arms  ICMJE Experimental: Auto- then Allo-HCT
Auto-HCT mobilization is cyclophosphamide 4 g/m2 + filgrastim 10 µg/kg/day for peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue [ie, autologous hematopoietic cells transplant (Auto-HCT)]. Post-infusion support is filgrastim 5 µg/kg/day, starting 6 days after melphalan. Stable/responsive disease at 4 weeks continues to allogenic HCT (Allo-HCT) from sibling donor fully-matched for human leukocyte antigen (HLA). Allo-HCT conditioning is total body irradiation (TBI) 200 centigray (cGy) + cyclosporine (CSP) 6.25 mg/kg + mycophenolate mofetil (MMF) 15 mg/kg. Donor mobilization is filgrastim 16 µg/kg/day on day -4 to Day 0; apheresis collections on Day -1 & Day 0, to a target of > 5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication hydrocortisone 100 mg IV & diphenhydramine 50 mg IV. CSP tapering on Day 56 to Day 180, adjusted as needed.
Interventions:
  • Procedure: Autologous hematopoietic cell transplant (Auto-HCT)
  • Procedure: Allogeneic hematopoietic cell transplant (Allo-HCT)
  • Drug: Cyclophosphamide
  • Drug: Filgrastim
  • Drug: Melphalan
  • Radiation: Total body irradiation (TBI)
  • Procedure: Cyclosporine (CSP)
  • Drug: Mycophenolate Mofetil (MMF)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 16, 2018)
63
Original Enrollment  ICMJE
 (submitted: September 12, 2005)
40
Actual Study Completion Date  ICMJE April 2010
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

PATIENT INCLUSION CRITERIA

  • Multiple myeloma, early Stage II-III or relapsed / progression after initial treatment of Stage I disease
  • Patient has HLA-identical sibling donor
  • Age ≤ 70 years
  • No prior therapy which would preclude the use of low-dose total body irradiation
  • Pathology review and diagnosis confirmation by Stanford University Medical Center
  • Karnofsky performance status (KPS) > 70%
  • DLCO ≥ 60% predicted
  • ALT and AST < 2 x upper limit of normal (ULN)
  • Total bilirubin < 2 mg/dL
  • Serum creatinine < 2.0, or 24-hour creatinine clearance ≥ 60 mL/min
  • HIV-negative
  • Signed informed consent document

PATIENT EXCLUSION CRITERIA

  • Smoldering multiple myeloma; monoclonal gammopathy of unknown significance; or primary amyloidosis
  • Severe psychological or medical illness
  • Prior allogeneic hematopoietic cell transplantation
  • Pregnant or lactating

ALLOGENEIC DONOR INCLUSION CRITERIA

  • Age ≥ 17
  • HIV-seronegative
  • Signed informed consent document

ALLOGENEIC DONOR EXCLUSION CRITERIA

  • Serious medical or psychological illness
  • Pregnant or lactating
  • Prior malignancies within the last 5 years, except for non-melanoma skin cancers
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00185614
Other Study ID Numbers  ICMJE IRB-13378
75190 ( Other Identifier: Stanford University Alternate IRB Approval No. )
BMT109 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wen-Kai Weng, Stanford University
Study Sponsor  ICMJE Wen-Kai Weng
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wen-Kai Weng, MD Stanford University
PRS Account Stanford University
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP