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Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies


Phase 1/Phase 2
18 Years
55 Years
Not Enrolling
Both
Hematologic Malignancy, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia in Blast Crisis, Anemia, Refractory, With Excess of Blasts, Chronic Myeloproliferative Disease, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Lymphoma, Large Cell Non-Hodgkin's Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, High Grade Non-Hodgkin's Lymphoma

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Trial Information

Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies


Based on prior studies, the first patient will start at lowest dose combination (3 x 10^6/kg
of Treg and 3 x 10^6/kg of CD3+ Teff cells).

One patient will be entered at each level with a minimum of 35 days to observe the patient
prior to moving to the next dose level. (1) If GVHD does not occur, a "successful step",
then the CD3+ Teff cell dose will increase to the next higher level for the next patient;
(2) If GVHD occurs, a "failed step", then Treg dose will increase to the next higher level
for the next patient. It would take a minimum of 5 (if no GVHD) and maximum of 9 patients
(if GVHD is observed at each level) to complete all Treg:CD3+ Teff cell combinations.

An additional 10 patients will be enrolled to verify that this reflects the optimal
combination and evaluate its safety profile.


Inclusion Criteria:



- Only patients requiring a double umbilical cord blood (UCB) transplant are to be
considered for this study.

UCB Requirements

- Three UCB units are required - one for Treg production and two for UCB transplant.
The unrelated UCB donors must be 4-6/6 HLA-A, B, DRB1 matched with the recipient (HLA
matching using molecular techniques: A and B to antigen level resolution and DR to
allele level resolution). Suitable UCB units will be selected according to the
University Of Minnesota UCB Graft Selection Algorithm.

- Suitable UCB units must be ABO matched.

Disease Criteria:

- Patients aged 18 to 55 years

- Acute Myeloid Leukemia: with morphologically persistent disease in a representative
bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy
(if patient refuses or is disqualified from alternative protocols), or in 3rd or
higher complete remission (CR).

- Acute Lymphocytic Leukemia: with morphologically persistent disease in a
representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles
of chemotherapy, or in 3rd or higher CR

- Chronic Myelogenous Leukemia in Blast Crisis: with ≤10% residual blasts in the bone
marrow aspirate after at least 1 cycle of induction chemotherapy in combination with
a tyrosine kinase inhibitor (TKI)

- Refractory Anemia with Excess Blasts: (≤ 10%) in representative bone marrow aspirate
sample of blasts after 1 cycle of induction chemotherapy. If treated with
hypomethylating agents, patients are eligible if blast count is ≤ 10% after 4 cycles
or evidence of stable or progressive disease after at least 2 cycles.

- Chronic Myeloproliferative Disease

- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Marginal Zone B-Cell
Lymphoma or Follicular Lymphoma: disease must be refractory after at least two
chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of
≥ 5 cm

- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia: disease
must be refractory after at least two chemotherapy regimens or is chemotherapy
sensitive but has residual nodal disease of ≥ 5 cm

- Large Cell Non-Hodgkin's Lymphoma: disease must be refractory after at least two
chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of
≥ 5 cm

- Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other High-Grade NHL: disease must be
refractory after at least two chemotherapy regimens or is chemotherapy sensitive but
has residual nodal disease of ≥ 5 cm

- Performance Status, Age, and Organ Function

- Adequate performance status defined as a Karnofsky score ≥ 80%

- Adequate organ function defined as:

- Renal: creatinine < 2.0 mg/dL,

- Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,

- Pulmonary function: DLCOcorr > 50% normal,

- Cardiac: left ventricular ejection fraction > 45%

- Voluntary written informed consent signed before performance of any study-related
procedure not part of normal medical care

Exclusion Criteria:

- Available medically suitable HLA-identical related donor

- Active infection at time of transplantation (including active infection with
Aspergillus or other mold within 30 days)

- History of HIV infection

- Pregnant or breast feeding. The agents used in this study may be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk.
Females of childbearing potential must have a blood test or urine study within 14
days prior to registration to rule out pregnancy

- Prior myeloablative transplant within the last 6 months

- Extensive prior therapy including > 12 months alkylator therapy or > 6 months
alkylator therapy with extensive radiation

- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar)
as part of their salvage therapy (not eligible for myeloablative umbilical cord blood
transplant)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal Cell Dose Mixture

Outcome Description:

Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD

Outcome Time Frame:

Day 0

Safety Issue:

Yes

Principal Investigator

Claudio Brunstein, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2009LS018

NCT ID:

NCT01163201

Start Date:

January 2014

Completion Date:

January 2015

Related Keywords:

  • Hematologic Malignancy
  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia in Blast Crisis
  • Anemia, Refractory, With Excess of Blasts
  • Chronic Myeloproliferative Disease
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Lymphoma
  • Large Cell Non-Hodgkin's Lymphoma
  • Lymphoblastic Lymphoma
  • Burkitt's Lymphoma
  • High Grade Non-Hodgkin's Lymphoma
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Burkitt Lymphoma
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Waldenstrom Macroglobulinemia
  • Myeloproliferative Disorders
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Hematologic Neoplasms

Name

Location

Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455