Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00185614
• Other study ID #: IRB-13378
• Secondary ID: 75190BMT109
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: January 16, 2018
• Start date: August 2000
• Est. completion date: April 2010

Study information

• Verified date: January 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: April 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood Cancer
• Hematologic Neoplasms
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Procedure:
• Autologous hematopoietic cell transplant (Auto-HCT)
The target cell dose is 2.6 x 10e6 CD34+ cells/kg
• 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
• 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)
• Melphalan
Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT

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

Drug:
• Mycophenolate Mofetil (MMF)
Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Wen-Kai Weng

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS)	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.	3 years
Secondary	Relapse Rate	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).	3 years
Secondary	Overall Survival (OS)	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 years
Secondary	Acute Graft-vs-Host-Disease (aGvHD)	Development of acute graft-vs-host-disease (aGvHD) within 6 months, for participants receiving Allo-HCT.	6 months
Secondary	Chronic Graft-vs-Host-Disease (cGvHD)	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).	3 years