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

Stanford University

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma

Blood and Marrow Transplant (BMT)

Transplantation, Autologous

Transplantation, Homologous

Treatments

Drug: Cyclophosphamide

Drug: Diphenhydramine

Drug: Solumedrol

Biological: Rabbit anti-thymocyte globulin

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

Drug: Cyclosporine

Drug: Hydrocortisone

Drug: Filgrastim

Radiation: Total lymphoid irradiation

Drug: Acetaminophen

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

Drug: Mycophenolate Mofetil 250mg

Drug: Melphalan

Study type

Interventional

Funder types

Other

Identifiers

NCT00899847

SU-04142009-2259 (Other Identifier)

BMT201 (Other Identifier)

IRB-15772

Details and patient eligibility

About

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

Full 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.

Enrollment

9 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

9 participants in 1 patient group

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Experimental group

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.

Treatment: