Regulatory T-Lymphocytes and Aldesleukin in Suppressing Acute Graft-Versus-Host-Disease after Umbilical Cord Blood Transplant in Patients with Hematological Malignancies

Status: Temporarily Closed to Accrual


This pilot phase II trial studies how well regulatory T-lymphocytes and aldesleukin work in suppressing acute graft-versus-host-disease (aGVHD) after umbilical cord blood transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood (UCB) transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving regulatory T-lymphocytes and aldesleukin after the transplant may stop this from happening.

Eligibility Criteria

Inclusion Criteria

  • Must be >= 18, but < 70 years of age with no matched 7/8 or 8/8 sibling donor - patients >= 70 and =< 75 years of age may be eligible if they have a co-morbidity score =< 2
  • UCB unit(s) composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm plus an additional cord blood unit to be used as the source to manufacture the Treg product; this UCB unit must be matched at 4-6/6 to the patient, considering HLA-A, B at the antigen level and DRB1 at the allele level
  • Acute leukemias: Must be in remission by morphology (=< 5% blasts); also a small percentage of blasts that is equivocal between marrow regeneration versus early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
  • Acute lymphoblastic leukemia (ALL) second or greater complete remission (CR); first complete remission (CR1) unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following: * Evidence of high risk cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1 * 30 years of age or older at diagnosis * White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis * Central nervous system (CNS) leukemia involvement during the course of disease * Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy) * Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
  • Acute myelogenous leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in =< 60 years old that is NOT considered as favorable-risk; favorable risk is defined as having one of the following: * t(8,21) without cKIT mutation * inv(16) or t(16;16) without cKIT mutation * Normal karyotype with mutated NPM1 and wild type FLT-ITD * Normal karyotype with double mutated CEBPA * Acute prolymphocytic leukemia (APL) in first molecular remission at end of consolidation
  • Biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR
  • Burkitt’s lymphoma in second complete remission (CR2) or subsequent CR
  • Chronic myelogenous leukemia: all types except refractory blast crisis; chronic phase patients must have failed at least two different tyrosine-kinase inhibitors (TKIs), or been intolerant to all available TKIs or have T315I mutation
  • Myelodysplastic syndrome: IPSS INT-2 or high risk; R-IPSS high or very high; World Health Organization (WHO) classification: RAEB-1, RAEB-2; severe cytopenias: absolute neutrophil count (ANC)0000 < 0.8, anemia or thrombocytopenia requiring transfusion; poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS; blasts must be < 5% by bone marrow aspirate morphology; if >= 5% blasts, patient requires chemotherapy for cytoreduction to < 5% blasts prior to transplantation
  • Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of achieving a partial or complete remission; patients who had remissions lasting > 12 months are eligible after at least two prior therapies; patients with bulky disease should be considered for debulking chemotherapy before transplant; patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month
  • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive
  • Patients must have undergone an autologous transplant =< 12 months prior to transplant on this study or have received multi-agent or immunosuppressive chemotherapy within 3 months of the preparative regimen
  • Karnofsky score >= 70%
  • Creatinine =< 2.0 mg/dL, for patient with a creatinine > 1.2 mg/dL or a history of renal dysfunction an estimated glomerular filtration rate >= 40 mL/min/1.73 m^2 is required
  • Iron (Fe) phosphatase =< 5 x upper limit of normal and total bilirubin =< 2.5 mg/dL except for patients with Gilbert’s syndrome or hemolysis
  • Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) >= 40% predicted, and absence of oxygen (O2) requirements
  • Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction >= 40%
  • Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
  • Voluntary written consent signed by the subject (or the subject’s legally authorized representative)

Exclusion Criteria

  • Untreated active infection
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breast feeding; females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
  • Prior allogeneic transplantation
  • Less than 3 months from myeloablative conditioning for autologous transplantation (if applicable)
  • Evidence of progressive disease by imaging modalities or biopsy - persistent positron emission tomography (PET) activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of computed tomography (CT) changes indicating progression
  • Chronic myelogenous leukemia (CML) in blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy
  • Active central nervous system malignancy

Locations & Contacts


University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Claudio Brunstein
Phone: 612-625-3918

Trial Objectives and Outline


I. To obtain preliminary estimate of efficacy as measured by the length of regulatory T cell (Treg) survival after infusion of Treg.

II. To evaluate the feasibility of this protocol in preparation for future larger scale studies as measured by the proportion of patients receiving the full course of aldesleukin (IL-2) treatment.


I. Probability of grade II-IV aGVHD.

II. Probability of grade III-IV aGVHD.

III. Probability of treatment related mortality (TRM) at 6 months.

IV. Probability of relapse at 1 year.

V. Probability of viral and fungal infections by 1 year.

VI. Pattern of immune reconstitution.

VII. The proportion of patients with detectable Treg cells at day 14 post infusion.

VIII. Toxicity.


I. Determine the incidence of chimerism at day +100.

II. Determine the probability of survival at 1 year.

III. Determine the incidence of neutrophil recovery at day 42.

IV. Determine the incidence of platelet recovery at 1 year.

V. Determine the incidence of chronic GVHD at 1 year.


PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients also undergo total body irradiation (TBI) on day -1.

GVHD PROPHYLAXIS: Patients receive sirolimus orally (PO) on days -3 to 100 and mycophenolate mofetil IV or PO on days -3 to 30.

UCB INFUSION: Patients undergo a double umbilical cord blood transplant and receive regulatory T-lymphocytes IV on day 0.

Patients then receive aldesleukin subcutaneously (SC) 3 times a week for 4 weeks.

After completion of study treatment, patients are followed up at 100 days, for 2 years, and then periodically thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Supportive care

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Claudio Brunstein

Trial IDs

Primary ID 2016LS107
Secondary IDs NCI-2017-00419 ID NCT02991898