Clinical trial NCT00185614: Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Official title: Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Blood Cancer
Multiple Myeloma
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Event-free Survival (EFS)
timeFrame: 3 years
Secondary outcomes:
measure: Relapse Rate
timeFrame: 3 years
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Acute Graft-vs-Host-Disease (aGvHD)
timeFrame: 6 months
measure: Chronic Graft-vs-Host-Disease (cGvHD)
timeFrame: 3 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Wen-Kai Weng, MD
role: PRINCIPAL_INVESTIGATOR
References: