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

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 \ 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.

Keywords: busulfan fludarabine g-csf melphalan rabbit atg wt1 peptide specific t cells 12-175