Brief Title
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies
Official Title
Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies
Brief Summary
This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB)
Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible
without conferring grade II-IV acute graft-versus-host disease (GVHD).
In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two
TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible
without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit
the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell
recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged
pharmacologic immunosuppression.
Detailed Description
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Optimal Cell Dose Mixture
Secondary Outcome
Determine incidence of infusional toxicity
Condition
Hematologic Malignancy
Intervention
Treg cells
Study Arms / Comparison Groups
Treg Plus CD3+Teff Treatment
Description: Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
0
Start Date
January 2014
Completion Date
January 2015
Primary Completion Date
January 2015
Eligibility Criteria
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)
Gender
All
Ages
18 Years - 55 Years
Accepts Healthy Volunteers
No
Contacts
Claudio Brunstein, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01163201
Organization ID
2009LS018
Secondary IDs
MT2009-03
Responsible Party
Sponsor
Study Sponsor
Masonic Cancer Center, University of Minnesota
Study Sponsor
Claudio Brunstein, MD, PhD, Principal Investigator, Masonic Cancer Center, University of Minnesota
Verification Date
November 2017