Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

• 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: Wen-Kai Weng
• Information provided by (Responsible Party): Wen-Kai Weng, Stanford University

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 16, 2005
• Results First Submitted Date: October 31, 2017
• Results First Posted Date: January 18, 2018
• Last Update Posted Date: January 18, 2018
• Study Start Date: August 2000
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Not Provided

Current Secondary Outcome Measures (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: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Blood Cancer
• Multiple Myeloma

Intervention

• 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

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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 16, 2018): 63
• Original Enrollment (submitted: September 12, 2005): 40
• Actual Study Completion Date: April 2010
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00185614
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Wen-Kai Weng, Stanford University
• Study Sponsor: Wen-Kai Weng
• Collaborators: Not Provided

Investigators

• Principal Investigator: Wen-Kai Weng, MD; Stanford University

• PRS Account: Stanford University
• Verification Date: January 2018