Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Wen-Kai Weng

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma

Blood Cancer

Treatments

Procedure: Allogeneic hematopoietic cell transplant (Allo-HCT)

Drug: Mycophenolate Mofetil (MMF)

Procedure: Autologous hematopoietic cell transplant (Auto-HCT)

Radiation: Total body irradiation (TBI)

Drug: Cyclophosphamide

Drug: Melphalan

Drug: Filgrastim

Procedure: Cyclosporine (CSP)

Study type

Interventional

Funder types

Other

Identifiers

NCT00185614

IRB-13378

75190 (Other Identifier)

BMT109 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

63 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

63 participants in 1 patient group

Auto- then Allo-HCT

Experimental group

Description:

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.

Treatment: