Clinical trial NCT01758328: 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
Official title: A Phase I 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: BUSULFAN
FLUDARABINE
G-CSF
MELPHALAN
RABBIT ATG WT1
PEPTIDE SPECIFIC T CELLS
12-175
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2013-01-01
Enrollment: 29
Sex: ALL
Minimum age (years): 21
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

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.

Primary outcomes:
measure: assess the toxicities
timeFrame: 21 days
measure: maximum tolerated dose (MTD)
timeFrame: 1 year
Secondary outcomes:
measure: serologic response
timeFrame: 2 years
measure: survival
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sergio Giralt, MD
role: PRINCIPAL_INVESTIGATOR
References: