Study Stopped
Slow accrual
Umbilical Cord Blood T-Regulatory Cell Infusion Followed by Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Leukemia or Other Hematologic Diseases
Umbilical Cord Blood Transplant With Co-Infusion of T Regulatory Cells
3 other identifiers
interventional
3
1 country
1
Brief Summary
RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal cells and prepares the patient's bone marrow for the stem 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. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Giving an infusion of the donor's T-regulatory cells before the transplant may help increase this effect. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of umbilical cord blood T-regulatory cell infusion followed by donor umbilical cord blood transplant in treating patients with high-risk leukemia or other hematologic diseases.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2007
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 13, 2006
CompletedFirst Posted
Study publicly available on registry
September 15, 2006
CompletedStudy Start
First participant enrolled
May 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2008
CompletedDecember 2, 2017
November 1, 2017
10 months
September 13, 2006
November 29, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose of T-regulatory cells
Dose limiting toxicities (DLT) are defined as any grade 3-4 toxicity within 24 hours of Treg cell infusion, excluding hematological .
Within 24 Hours
Secondary Outcomes (6)
Incidence of neutrophil recovery
Day 42
Incidence of double chimerism
Day 21
Incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD)
Day 100
Incidence of chronic graft-versus-host disease
1 Year
Survival
Day 100 and 1 Year
- +1 more secondary outcomes
Study Arms (1)
Transplant with Treg Cells
EXPERIMENTALPatients receive preparative therapy with Fludarabine, cyclophosphamide, total body irradiation and Treg infusion followed by umbilical cord blood transplantation.
Interventions
Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush and mesna (MT(S)9006) on day -8 and -7 one hour after fludarabine infusion.
Will be administered beginning on day -3 and adjusted to maintain a level of \>200. For adults the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours.
Fludarabine 25 mg/m\^2/day will be administered as a 1 hour intravenous infusion on days -9 through -7.
All patients will begin mycophenolate mofetil (MMF) on day -3, at the dose of 3 grams/day divided into 2 or 3 doses (every 12 or 8 hours).
On day -1 prior to UCB transplantation, Treg cells will be infused IV without in-line filtration. A semi-log dose escalation of CD4+CD25+ Treg cells is scheduled with 3 patients at each step. Doses will be 0.1 x 10\^6/kg, 0.3 x 10\^6/kg, 1 x 10\^6/kg and 3 x 10\^6/kg weight (determined on the day prior to administration of the preparative therapy).
Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. The UCB will be administrated by IV infusion without in-line filtration.
Radiotherapy: 165 cGy will be administered on day -5 through -2 two fractions each day.
Eligibility Criteria
You may qualify if:
- Patient and Donor Demographic Criteria
- Patient must be 18-45 years of age.
- Patients must have three partially HLA matched UCB units. Units identified as the HSC source must be HLA matched at 4-6 HLA- A and B (at low to intermediate resolution) and DRB1 (at high resolution), and the units must be HLA matched at 4-6 HLA- A, B, DRB1 antigens with each other. Total cryopreserved HSC graft cell dose must be \>2.5 x 107 nucleated cells per kilogram recipient body weight. Also, the two umbilical cord blood (UCB) units must be ABO-matched.
- The UCB unit identified as the Treg source must be HLA matched at 4-6 HLA antigens with the patient (without an HLA or ABO matching criterion with the UCB HSC source).
- Disease Criteria
- Patients must have a hematological malignancy as listed below:
- Acute myelogenous leukemia: high risk CR1 (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, or \>2 cycles to obtain complete remission (CR); second or greater CR. Must be in remission by morphology (\<5% blasts within normocellular marrow).
- Acute lymphocytic leukemia: high risk CR1 as evidenced by high risk cytogenetics \[t(9;22), t (1:19), t(4;11) or other MLL rearrangements\] or \> 1 cycle to obtain CR; second or greater CR.
- Chronic myelogenous leukemia resistant to imatinib therapy
- Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be \< 10% by a representative bone marrow aspirate morphology (otherwise induction chemotherapy to achieve \< 10% blasts is required pre-transplant).
- Advanced myelofibrosis
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+.
- Large cell non-Hodgkins lymphoma (NHL) \> CR2/\> PR2. Patients in CR2/PR2 with initial short remission(\<6 months) are eligible.
- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II \<1 year.
- +3 more criteria
You may not qualify if:
- Pregnant or breastfeeding
- Evidence of HIV infection or known HIV positive serology
- Current active infection
- Available HLA matched sibling donor.
- CML in active blast crisis
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Claudio G. Brunstein, MD, PhD
Masonic Cancer Center, University of Minnesota
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2006
First Posted
September 15, 2006
Study Start
May 1, 2007
Primary Completion
March 1, 2008
Study Completion
March 1, 2008
Last Updated
December 2, 2017
Record last verified: 2017-11