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

NCT ID: NCT01758328

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2025-03-17

Brief 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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pts with Mutiple myeloma

Patients will undergo a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor. Hematopoietic stem cell donors for this trial will include individuals who are 10/10 HLA matched or one antigen or allele mismatched at the HLA-A, B, C, DRB1 or DQB1 locus, as defined by high resolution methods .Donors who are 8/10 HLA matched with an antigen or allele mismatched at HLA-DQB1 and at one other locus will also be eligible for the trial. The administration of WT1-specific cytotoxic T cells (WT1 CTLs) post transplantation is integrated to induce complete remissions in patients with residual disease and to decrease the rate of relapse following the allogeneic transplant.

Group Type: EXPERIMENTAL

busulfan

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

fludarabine

Intervention Type: DRUG

anti-thymocyte globulin (ATG)

Intervention Type: BIOLOGICAL

a T cell depleted stem cell transplant

Intervention Type: PROCEDURE

Interventions

busulfan

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

fludarabine

Intervention Type: DRUG

anti-thymocyte globulin (ATG)

Intervention Type: BIOLOGICAL

a T cell depleted stem cell transplant

Intervention Type: PROCEDURE

Eligibility 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.

• 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Giralt, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

12-175

Identifier Type: -

Identifier Source: org_study_id