Hematologic MalignancyPhase 1/2NCT01163201
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies
A Phase 1/2 study testing Treg cells, CD3+ Teff cells and Fludarabine in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Hematologic Malignancy, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
- What is being tested?
- Treg cells, CD3+ Teff cells and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Jan 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 23Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55445
About this study
Official title: Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies
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.
Read the 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.
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia in Blast Crisis, Anemia, Refractory, With Excess of Blasts, Chronic Myeloproliferative Disease
- Being tested
- Treg cells, CD3+ Teff cells, Fludarabine, Cyclophosphamide, Total body irradiation
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Anemia, Refractory, with Excess of Blasts, Myeloproliferative Disorders, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treg cellsBiological
Given by infusion on Day 0 after transplantation - Five doses of Treg (3 x 10^6/kg, 10 x 10^6/kg, 30 x 10^6/kg, 100 x 10^6/kg and 300 x 10^6/kg)
CD3+ Teff cellsBiological
Given by infusion on Day 0 after transplantation - 5 doses of CD3+ Teff cells (3 x 10^6 cells/kg, 6 x 10^6 cells/kg, 9 x 10^6 cells/kg, 12 x 10^6 cells/kg, and 15 x 10^6 cells/kg with the latter dose representing the median number of CD3+ cells in two UCB unit grafts
FludarabineDrug
Also called Fludara
Given intravenously on Days -8 through -6, 25 mg/m^2 over 1 hour
CyclophosphamideDrug
Also called Cytoxan
Given intravenously on Day -7 and -6, 60 mg/kg
Total body irradiationRadiation
Given on Days -4 through -2, 165 cGY twice a day.
Umbilical cord blood transplantationBiological
Also called UCBT
Infusion given on day 0
| Study group | Role | What they receive |
|---|---|---|
| Treg Plus CD3+Teff Treatment | Experimental | Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation Receives: Biological: Treg cells; Biological: CD3+ Teff cells; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Biological: Umbilical cord blood transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal Cell Dose Mixture
Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD
Measured: Day 0
Secondary outcomes (10)
Determine incidence of infusional toxicity
reaction that occurs with 48 hours of product infusion
Measured: 48 hours
Incidence of neutrophil recovery
Determine the incidence of neutrophil recovery (absolute neutrophil count ≥ 500/uL) at day 42
Measured: Day 42
Incidence of double and single chimerism
Determine incidence of double and single unit chimerism at various time points
Measured: Day +21, Day +180, 1 Year
Incidence of Viral and Fungal Infections
Determine incidence of viral and fungal infections at 1 year
Measured: 1 Year
1 Year Survival
Estimate the probability of survival at 1 year
Measured: 1 Year
Incidence of Grade III-IV Acute Graft-Versus-Host Disease
Determine the incidence of grade III-IV acute GVHD at day 100
Measured: Day 100
Incidence of Treatment Related Death
Determine the incidence of treatment related mortality (TRM) at 6 months
Measured: 6 Months
Incidence of Platelet Recovery
Determine the incidence of platelet recovery (platelet count ≥ 50,000/uL) at 1 year
Measured: 1 Year
Incidence of Chronic Graft-Versus-Host Disease
Determine the incidence of chronic GVHD at 1 year
Measured: 1 Year
Incidence of Relapse
Determine the incidence of relapse at 1 year
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2010 (estimated)
- Study startJan 2014
- Primary completionJan 2015 (estimated)
- Study completionJan 2015 (estimated)
Why it stopped: Replaced by a new study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claudio Brunstein, MD, PhD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01163201
- Sponsor's protocol ID
- 2009LS018
- Other IDs
- MT2009-03, 0910M73595
- Status last verified
- Nov 2017
- First submitted
- 26 May 2010
- Last updated
- 2 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies
- ClinicalTrials.gov ID
- NCT01163201
- Acronym / sponsor ID
- 2009LS018
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia in Blast Crisis, Anemia, Refractory, With Excess of Blasts, Chronic Myeloproliferative Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Replaced by a new study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Jan 2015 (estimated)
- Study completion
- Jan 2015 (estimated)
- First posted
- 15 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treg Plus CD3+Teff Treatment | Experimental | Biological: Treg cells, Biological: CD3+ Teff cells, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total body irradiation, Biological: Umbilical cord blood transplantationIncludes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- 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.
- Patients aged 18 to 55 years
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treg cellsGiven by infusion on Day 0 after transplantation - Five doses of Treg (3 x 10^6/kg, 10 x 10^6/kg, 30 x 10^6/kg, 100 x 10^6/kg and 300 x 10^6/kg) | Biological | Treg Plus CD3+Teff Treatment |
| CD3+ Teff cellsGiven by infusion on Day 0 after transplantation - 5 doses of CD3+ Teff cells (3 x 10^6 cells/kg, 6 x 10^6 cells/kg, 9 x 10^6 cells/kg, 12 x 10^6 cells/kg, and 15 x 10^6 cells/kg with the latter dose representing the median number of CD3+ cells in two UCB unit grafts | Biological | Treg Plus CD3+Teff Treatment |
| FludarabineAlso: FludaraGiven intravenously on Days -8 through -6, 25 mg/m^2 over 1 hour | Drug | Treg Plus CD3+Teff Treatment |
| CyclophosphamideAlso: CytoxanGiven intravenously on Day -7 and -6, 60 mg/kg | Drug | Treg Plus CD3+Teff Treatment |
| Total body irradiationGiven on Days -4 through -2, 165 cGY twice a day. | Radiation | Treg Plus CD3+Teff Treatment |
| Umbilical cord blood transplantationAlso: UCBTInfusion given on day 0 | Biological | Treg Plus CD3+Teff Treatment |
Primary outcome
Optimal Cell Dose Mixture
Time frame: Day 0
Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD
10 secondary outcomes
Determine incidence of infusional toxicity
Time frame: 48 hours
Incidence of neutrophil recovery
Time frame: Day 42
Incidence of double and single chimerism
Time frame: Day +21, Day +180, 1 Year
Incidence of Viral and Fungal Infections
Time frame: 1 Year
1 Year Survival
Time frame: 1 Year
Incidence of Grade III-IV Acute Graft-Versus-Host Disease
Time frame: Day 100
Incidence of Treatment Related Death
Time frame: 6 Months
Incidence of Platelet Recovery
Time frame: 1 Year
Incidence of Chronic Graft-Versus-Host Disease
Time frame: 1 Year
Incidence of Relapse
Time frame: 1 Year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudio Brunstein, MD, PhD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Treg cells, CD3+ Teff cells and Fludarabine in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal Cell Dose Mixture (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.