ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.

Condition or disease Intervention/treatment Phase
Blood Cancer Multiple Myeloma 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) Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Study Start Date : August 2000
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00185614


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Wen-Kai Weng
Investigators
Principal Investigator: Wen-Kai Weng, MD Stanford University

Responsible Party: Wen-Kai Weng, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00185614     History of Changes
Other Study ID Numbers: IRB-13378
75190 ( Other Identifier: Stanford University Alternate IRB Approval No. )
BMT109 ( Other Identifier: OnCore )
First Posted: September 16, 2005    Key Record Dates
Results First Posted: January 18, 2018
Last Update Posted: January 18, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Cyclophosphamide
Cyclosporins
Cyclosporine
Melphalan
Mycophenolic Acid
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents