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

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

Sponsors

Lead Sponsor: Stanford University

Source Stanford University
Brief Summary

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

Detailed 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.

Overall Status Completed
Start Date 2009-05-01
Completion Date 2014-12-01
Primary Completion Date 2014-04-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of Graft Versus Host Disease (GvHD) 2 years after the last participant is enrolled.
Secondary Outcome
Measure Time Frame
Median Time to Engraftment After Auto-PBSC Transplant 1 month
Median Time to Engraftment After Allo-PBSC Transplant 1 month
Overall Response Rate (ORR) 1 year
Complete Response Rate (CRR) 1 year
Partial Response Rate (PRR) 1 year
Event-free Survival (EFS) 2 years after the last participant is enrolled
Overall Survival (OS) 2 years after the last participant is enrolled
Enrollment 9
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Autologous peripheral blood stem cells (auto-PBSC) transplantation

Description: 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

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Procedure

Intervention Name: Allogeneic peripheral blood stem cells (allo-PBSC) transplantation

Description: Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Filgrastim

Description: 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.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Melphalan

Description: Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Cyclosporine

Description: 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.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Radiation

Intervention Name: Total lymphoid irradiation

Description: 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.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Other Name: TLI

Intervention Type: Biological

Intervention Name: Rabbit anti-thymocyte globulin

Description: ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Mycophenolate Mofetil 250mg

Description: 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

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Solumedrol

Description: Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Intervention Type: Drug

Intervention Name: Diphenhydramine

Description: Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Other Name: Benadryl

Intervention Type: Drug

Intervention Name: Acetaminophen

Description: Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Other Name: Tylenol

Intervention Type: Drug

Intervention Name: Hydrocortisone

Description: Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Arm Group Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

75 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Wen-Kai Weng Principal Investigator Stanford University
Location
Facility: Stanford University School of Medicine
Location Countries

United States

Verification Date

2017-09-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Stanford University

Investigator Full Name: Wen-Kai Weng

Investigator Title: Assistant Professor of Medicine (Blood and Marrow Transplantation)

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Type: Experimental

Description: Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control. Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion. For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC. Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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