Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

Multiple Myeloma Clinical Trial

Official title:

A Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) in Multiple Myeloma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00899847
• Other study ID #: IRB-15772
• Secondary ID: SU-04142009-2259
• Status: Completed
• Phase: Phase 2
• First received: May 8, 2009
• Last updated: September 19, 2017
• Start date: May 2009
• Est. completion date: December 2014

Study information

• Verified date: September 2017
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

Description:

Development of cell-based immunotherapy from allogeneic hematopoietic cell transplantation (HCT) is dependent upon stable T-cell engraftment and the success of this therapeutic approach is likely to be greatest when directed against a minimal rather than gross tumor burden. To this end, tandem transplants with high dose therapy and autologous hematopoietic cell transplantation (AHCT) for tumor cytoreduction followed by non-myeloablative allotransplant have been conducted. In myeloma, this tandem approach results in greater efficacy compared to conventional AHCT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

PARTICIPANT INCLUSION CRITERIA

• Stage II-III multiple myeloma or have progression after initial treatment of Stage I disease (Durie Salmon Staging). Patients with plasma cell leukemia are also included.

• Multiple myeloma / plasma cell leukemia diagnosis confirmed by pathology reviewed at Stanford University Medical Center.

• 18 to = 75 years of age

• Karnofsky Performance Status > 70%.

• Corrected Carbon monoxide diffusing capacity (Dlco) > 60%

• Left ventricle ejection fraction (LVEF) > 50%.

• Alanine aminotransferase (ALT) = 2 x normal

• Aspartate aminotransferase (AST) = 2 x normal

• Total bilirubin = 2 mg/dL, unless hemolysis or Gilbert's disease.

• Estimated creatinine clearance > 50 mL/min.

• Identified related or unrelated Human leukocyte antigen (HLA)-identical donor or donor with one antigen/allele mismatch in (HLA-A, B, C or DRB1).

• Signed informed consent.

DONOR INCLUSION CRITERIA

• At least 17 years of age

• HIV-seronegative

• Must be capable of giving signed, informed consent

• No contraindication to the administration of filgrastim

• Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate

PARTICIPANT EXCLUSION CRITERIA

• Prior allogeneic hematopoietic cell transplantation

• Uncontrolled active infection

• Uncontrolled congestive heart failure or angina

• HIV-positive

• Pregnant or nursing

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 and Marrow Transplant (BMT)
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Transplantation, Autologous
• Transplantation, Homologous

Intervention

Procedure:
• Autologous peripheral blood stem cells (auto-PBSC) transplantation
Auto-PBSC = 2 to 3 x 10e6 CD34+ cells/kg are intravenously (IV) infused as part of the combination stem cell therapy. and allogeneic stem cells are administered intravenous (IV) infusion to reestablish hematopoietic function in patients whose bone marrow or immune system is damaged or defective
• Allogeneic peripheral blood stem cells (allo-PBSC) transplantation
Allo-PBSC (target collection = 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.

Drug:
• Filgrastim
Filgrastim is administered subcutaneously (SC) at 10 µg/kg/day for auto-PBSC mobilization starting day 2 of mobilization until the last day of apheresis. Filgrastim is administered SC at 5 µg/kg/day from Day 6 after auto-PBSC infusion to hematologic recovery. Filgrastim is administered SC at 16 µg/kg/day for donor allo-PBSC mobilization at from Day - 4 to Day 0, prior to allo-PBSC collection.
• Cyclophosphamide
Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.
• Melphalan
Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.
• Cyclosporine
Cyclosporine is administered by mouth (PO) for allo-PBSC graft vs host disease (GvHD) prophylaxis at 5 mg/kg from Day -3 through Bay +56. Tacrolimus may substituted.

Radiation:
• Total lymphoid irradiation
Total lymphoid irradiation is administered at 80 centigrey (cGy) on Day -11 to -7; and Day -4 to -2 before alllo-PBSC infusion. TLI is also administered at 80 centigrey (cGy) x 2 on Day -1 before alllo-PBSC infusion.

Biological:
• Rabbit anti-thymocyte globulin
ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.

Drug:
• Mycophenolate Mofetil 250mg
MMF is administered at 15 mg/kg 3x/day by mouth (PO) after allo-PBSC through Day 40, followed by 10% dose reduction weekly (dose taper) through day 96, and adjusted if there is evidence of MMF-related GI toxicity or excessive myelosuppression
• Solumedrol
Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion
• Diphenhydramine
Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.
• Acetaminophen
Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.
• Hydrocortisone
Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Graft Versus Host Disease (GvHD)	To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting	2 years after the last participant is enrolled.
Secondary	Median Time to Engraftment After Auto-PBSC Transplant	Engraftment is assessed as: Neutrophil engraftment is > 0.5 x 10?/L after cytopenia; Platelet engraftment is > 20 x 10?/L after cytopenia	1 month
Secondary	Median Time to Engraftment After Allo-PBSC Transplant	Engraftment is assessed as: Neutrophil engraftment is > 0.5 x 10?/L after cytopenia; Platelet engraftment is > 20 x 10?/L after cytopenia	1 month
Secondary	Overall Response Rate (ORR)	Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)	1 year
Secondary	Complete Response Rate (CRR)	Complete response rate (CRR) was assessed as all of: Negative immunoflixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; < 5% plasma cells in bone marrow	1 year
Secondary	Partial Response Rate (PRR)	Partial response rate (PRR) was assessed as; > 50% reduction in serum M-protein plus urine M-protein reduction by 90% or < 200 mg/24 hr; If serum M-protein is not measurable, then > 50% reduction in the involved serum free light chain; If involved serum free light chain is not measurable, then > 50% reduction in the bone marrow plasma cell percentage + > 50% reduction in the size of any soft tissue plasmacytoma.	1 year
Secondary	Event-free Survival (EFS)	To evaluate the graft versus myeloma effect by monitoring rate of event-free survival (EFS)	2 years after the last participant is enrolled
Secondary	Overall Survival (OS)	To evaluate the graft versus myeloma effect by monitoring rate of overall survival (OS)	2 years after the last participant is enrolled