Patient case: 60-year-old male with melanoma; genetic feature: NTRK1 rearrangement

Clinical trial: Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation

Summary: This is a phase I single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory T cells (iTregs) when given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5 dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.

Detailed description: Co-enrollment in University Of Minnesota protocol MT2001-10 is required and transplantation will be according to that protocol with iTregs administered the morning of day 0 followed no sooner than 4 hours later by the PBSC transplantation.

Eligibility: Inclusion Criteria:
  -  18 - 75 years of age with an HLA-identical sibling donor
  -  One of the following disease categories:
  -  Acute myelogenous leukemia - high risk CR1 (as evidenced by preceding MDS, intermediate to high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
  -  Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or >1cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
  -  Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)
  -  Non-Hodgkin lymphoma or Hodgkin lymphoma demonstrating chemosensitive disease
  -  Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
  -  Performance status: Karnofsky ≥ 60%
  -  Adequate organ function within 28 days of study enrollment defined as:
  -  Liver: SGOT and SGPT < 5.0 x ULN; total bilirubin < 3 x ULN
  -  Renal: serum creatinine < 2.0 mg/dl or glomerular filtration rate (GFR) > 40 mL/min/1.73m2. Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2
  -  Albumin: > 2.5 g/dL
  -  Cardiac: No decompensated CHF or uncontrolled arrhythmia; ejection fraction > 35% within 6 weeks prior to study enrollment
  -  Pulmonary: No O2 requirements; DLCO > 30% predicted within 6 weeks prior to study enrollment
  -  If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
  -  Sexually active females of child bearing potential and males must agree to use effective contraception for the duration of the transplant period
  -  Voluntary written consent
  Exclusion Criteria:
  -  Pregnancy or breast feeding - women of childbearing potential must have a negative pregnancy test within 28 days of study enrollment.
  -  Prior myeloablative transplant within previous 3 months of study enrollment.
  -  Evidence of HIV infection or known HIV positive serology.
  -  Active serious infection.

Relevance to patient case: not relevant