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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Procedure: a T cell depleted stem cell transplant; Drug: busulfan; Biological: anti-thymocyte globulin (ATG); Drug: fludarabine; Drug: melphalan

Study type: Interventional

Funder types: Other

Identifiers

NCT01758328

12-175

Details and patient eligibility

About

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.

Enrollment: 29 patients

Sex: All

Ages: 21 to 72 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Pts with Mutiple myeloma

Experimental group

Description:

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.

Treatment:

Drug: melphalan

Drug: fludarabine

Biological: anti-thymocyte globulin (ATG)

Drug: busulfan

Procedure: a T cell depleted stem cell transplant