Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Conditions: Keywords
BUSULFAN, FLUDARABINE, G-CSF, MELPHALAN, RABBIT ATG WT1, PEPTIDE SPECIFIC T CELLS, 12-175
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: busulfan Type: Drug
Name: melphalan Type: Drug
Name: fludarabine Type: Drug
Name: anti-thymocyte globulin (ATG) Type: Biological
Name: a T cell depleted stem cell transplant Type: Procedure
Overall Status
Recruiting
Summary
The purpose of this study is to test the safety of specialized white cells from the donor at different doses. They are called WT1 sensitized T cells. They have been grown in the lab and are immunized against a protein. The protein is called the Wilms' tumor protein, or WT1. The multiple myeloma cells make and express this protein". The investigators want to learn whether the WT1 sensitized T cells will attach to the protein and kill the myeloma cells. The investigators want to find out what effects, good and/or bad, it has on the patient and multiple myeloma.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 72 Years
Minimum Age: 21 Years
Gender: Both
Criteria: Inclusion Criteria:

Diagnosis:

- Patient must have multiple myeloma that has either relapsed or remains refractory following autologous stem cell transplantation and patients who have plasma cell leukemia at diagnosis.

- Patients with relapsed multiple myeloma following autologous stem cell transplantation who achieved < partial response following additional chemotherapy or who achieved < PR at 3 months following autologous stem cell transplantation and patients with plasma cell leukemia at diagnosis.

DONOR: Patients must have a healthy HLA matched or mismatched related or unrelated donor who is willing to receive G-CSF injections and undergo apheresis for PBSC collection, or undergo a marrow harvesting procedure.

- HLA-matched related and unrelated donors Patients who have an HLA-matched related or unrelated donor are eligible for entry on this protocol. This will include a healthy donor who is genotypically matched at all A, B, C, DRB1 and DQB1 loci, as tested by DNA analysis.

- HLA- mismatched related and unrelated donors

- Patients who do not have an HLA-matched donor but have a related or unrelated donor who have one antigen or one allele mismatch at the HLA A, B, C, DRB1 or DQB1 loci or who have two mismatches, at HLA-DQB1 and at one other locus, will be eligible for entry on this protocol.

The following inclusion criteria are also required:

- Patients should be ≥ 21, < 73 years old.

- Patients may be of either gender or any ethnic background.

- Patients must have a Karnofsky (adult) or Performance Status > 70%

- Patients must have adequate organ function measured by:

1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.

2. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.

3. Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min.

4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

- Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

- Female patients who are pregnant or breast-feeding

- Active viral, bacterial or fungal infection

- Patient seropositive for HIV-I/II; HTLV -I/II

- Patients who have had a previous malignancy that is not in remission.

- Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving SBA-E- bone marrow, or chicken egg products.
Location
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Status: Recruiting
Contact: Guenther Koehne, MD, PhD - 212-639-8599
Start Date
December 2012
Completion Date
December 2016
Sponsors
Memorial Sloan Kettering Cancer Center
Source
Memorial Sloan Kettering Cancer Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page