Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

NCT ID: NCT00185614

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-08-31
• Study Completion Date: 2010-04-30

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.

Conditions

Blood Cancer; Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Autologous hematopoietic cell transplant (Auto-HCT)

Intervention Type: PROCEDURE

The target cell dose is 2.6 x 10e6 CD34+ cells/kg

Allogeneic hematopoietic cell transplant (Allo-HCT)

Intervention Type: PROCEDURE

The target cell dose is 5 x 10e6 CD34 cells/kg

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion

Filgrastim

Intervention Type: DRUG

• 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

Intervention Type: DRUG

Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT

Total body irradiation (TBI)

Intervention Type: RADIATION

200 centigray (cGy) total body irradiation delivered on Day 0

Cyclosporine (CSP)

Intervention Type: PROCEDURE

Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56

Mycophenolate Mofetil (MMF)

Intervention Type: DRUG

Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27

Interventions

Autologous hematopoietic cell transplant (Auto-HCT)

The target cell dose is 2.6 x 10e6 CD34+ cells/kg

Intervention Type: PROCEDURE

Allogeneic hematopoietic cell transplant (Allo-HCT)

The target cell dose is 5 x 10e6 CD34 cells/kg

Intervention Type: PROCEDURE

Cyclophosphamide

Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion

Intervention Type: 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)

Intervention Type: DRUG

Melphalan

Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT

Intervention Type: DRUG

Total body irradiation (TBI)

200 centigray (cGy) total body irradiation delivered on Day 0

Intervention Type: RADIATION

Cyclosporine (CSP)

Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56

Intervention Type: PROCEDURE

Mycophenolate Mofetil (MMF)

Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27

Intervention Type: DRUG

Other Intervention Names

Cytoxan; Neosar; Neupogen; Granulocyte-colony stimulating factor (G-CSF); Melphalan hydrochloride; Melphalan HCl; Cyclosporine A; CellCept

Eligibility Criteria

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

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

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

• Serious medical or psychological illness
• Pregnant or lactating
• Prior malignancies within the last 5 years, except for non-melanoma skin cancers

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wen-Kai Weng

OTHER

Sponsor Role: lead

Responsible Party

Wen-Kai Weng

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wen-Kai Weng, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

75190

Identifier Type: OTHER

Identifier Source: secondary_id

BMT109

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-13378

Identifier Type: -

Identifier Source: org_study_id