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Hematologic MalignanciesPhase 2NCT02118311

Treg Cells for AGVHD in Non-myeloablative UCB Transplant

A Phase 2 study testing T Regulatory cells, Fludarabine and Cyclophosphamide in people with Hematologic Malignancies, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a Simon's optimal two-stage phase II trial designed to estimate grade II-IV acute graft-versus-host disease (GVHD) after infusion of T regulatory (nTreg) in a fixed dose ratio to the combined CD3+ cell count of the two graft units in recipients of double UCB transplantation. Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Hematologic Malignancies
What is being tested?
T Regulatory cells, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jun 2016to Sep 2018
Phase
Phase 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 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must be ≥18, but < 70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (Appendix II)
  • Three UCB units composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm.
  • Each UCB unit must be matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. This may include 0-2 antigen mismatches at the A or B or DRB1 loci. Each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, not necessarily at the same loci they are matched to the recipient.
  • Disease Criteria
  • Acute Leukemias: Must be in remission by morphology (<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. 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) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following:
Show all 33Show fewer
  • Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements
  • White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
  • Recipient age older than 30 years at diagnosis
  • Time to CR greater than 4 weeks
  • Acute Myelogenous Leukemia (AML) in first complete remission (CR1) 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) without CKIT mutation or t(16;16)
  • Normal karyotype with mutated NPM1 and not FLT-IND
  • Normal karyotype with double mutated CEBPA
  • APL in first molecular remission at end of consolidation
  • Acute Leukemias in 2nd or subsequent CR
  • Biphenotypic/Undifferentiated in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent complete remission (CR)
  • Burkitt's Lymphoma in CR2 or subsequent complete remission (CR)
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia: all types except refractory blast crisis. Chronic phase patients must have failed or been intolerant to at least one tyrosine-kinase inhibitor
  • Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe pancytopenia or complex cytogenetics. Blasts must be less than 5%. If 5% or more requires induction therapy pre-transplant to reduce blast count to ≤5%.
  • 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 allogeneic transplantation or have received multi-agent or immunosuppressive chemotherapy within 3 months of the preparative regimen.
  • Adequate performance status defined as a Karnofsky score ≥ 70%
  • Adequate organ function within 14 days (30 days for cardiac and pulmonary) of enrollment defined as:
  • Renal: 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 m2 is required
  • Hepatic: bilirubin, AST, ALT, alkaline phosphatase < 5 x upper limit of normal,
  • Pulmonary function: DLCOcorr > 40% normal,
  • Cardiac: left ventricular ejection fraction > 35%
  • Voluntary written consent signed before performance of any study-related procedure not part of normal medical care

Who cannot join

  • Untreated active infection at time of transplantation
  • 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 allogeneic transplantation
  • Less than 3 months from myeloablative conditioning for autologous transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Minnesota Masonic Cancer Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: T Regulatory Cell for Suppression of Acute Graft-vs-Host-Disease in Recipients of a Non-Myeloablative Umbilical Cord Blood Transplantation for Treatment of Hematological Malignancies

This is a Simon's optimal two-stage phase II trial designed to estimate grade II-IV acute graft-versus-host disease (GVHD) after infusion of T regulatory (nTreg) in a fixed dose ratio to the combined CD3+ cell count of the two graft units in recipients of double UCB transplantation. The nTreg cells (manufactured from a 3rd cord blood unit) are infused on day 0 at least 1 hour after the 2nd unit of the double umbilical cord blood (UCB) transplant.

The nTreg cells require an 18 day (±2 days) lead time based on the planned transplant day. The combined CD3+ cell content from the two graft UCB units is enumerated upon thaw (day 0). The patient then receives the number of nTregs cells from the 3rd cord product to achieve a Treg:CD3+ cells ratio of 5:1. The nTreg cell dose depends on the CD3+ cell content of the two graft UCB graft units, but it will not exceed the highest dose level safely tested in the ongoing University of Minnesota phase I Treg dose escalation study MT 2006-01.

Being tested
T Regulatory cells, Fludarabine, Cyclophosphamide, Total Body Irradiation
Keywords
Acute Leukemias, Burkitt's Lymphoma, Natural Killer Cell Malignancies, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome, Large-Cell Lymphoma, Hodgkin Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma:, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia
Medical subject headings
Hematologic Neoplasms, Burkitt Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Dendritic Cell Sarcoma, Interdigitating, Hodgkin Disease, Multiple Myeloma, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T Regulatory cellsBiological

    Also called nTreg, Treg

    Fixed dose of nTreg cells will be infused on day 0 of transplant after the umbilical cord blood cells

  • FludarabineDrug

    Also called Fludara

    Fludarabine 30mg/m^2 IV over 1 hour on days -6 through -2 from transplant

  • CyclophosphamideDrug

    Also called Endoxan, Cytoxan, Neosar, Procytox

    Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 from transplant

  • Total Body IrradiationRadiation

    Also called TBI

    Total Body Irradiation (TBI) 200 cGy administered on day -1 in a single fraction will be given at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.

Study groups in NCT02118311
Study groupRoleWhat they receive
TREGExperimentalT regulatory cells after non-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.
Receives: Biological: T Regulatory cells; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation
Non-Myeloablative OnlyExperimentalNon-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of grade II-IV acute graft-versus-host disease

    Determine if 3:1 ratio of Treg:CD3+ cells reduces the risk grade II-IV acute graft versus host disease of 20% by day 100 as compared to patients with hematological malignancy receiving same conditioning regimen and immunosuppression but no Tregs.

    Measured: Day +100

Secondary outcomes (9)

  1. Incidence of double and single unit chimerism

    Compare the incidence of double and single unit chimerism at day +100 between Treg and controls

    Measured: Day +100

  2. Incidence of grade III-IV acute graft-versus-host disease

    Compare the incidence of grade III-IV aGVHD between Treg and controls

    Measured: Day +100

  3. Incidence of viral and fungal infections

    Compare the incidence of viral and fungal infections at 1 year between Treg and controls

    Measured: 1 year

  4. Survival

    Compare the probability of survival at 1 year between Treg and controls

    Measured: 1 year

  5. Incidence of neutrophil recovery

    Compare the incidence of neutrophil recovery at day 42 between Treg and controls

    Measured: Day 42

  6. Incidence of treatment related mortality

    Determine the incidence of treatment related mortality (TRM) at 6 months between Treg and controls

    Measured: 6 months

  7. Incidence of platelet recovery

    Compare the incidence of platelet recovery at 1 year between Treg and controls

    Measured: 1 year

  8. Incidence of chronic GVHD

    Compare the incidence of chronic GVHD at 1 year between Treg and controls

    Measured: 1 year

  9. Incidence of relapse

    Compare the incidence of relapse at 1 year between Treg and controls

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2014 (estimated)
  2. Study startJun 2016
  3. Primary completionSep 2018 (estimated)
  4. Study completionSep 2018 (estimated)

Why it stopped: Changing study design. Will replace with a different protocol.

Resources

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 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02118311
Sponsor's protocol ID
2013LS091
Other IDs
MT2013-27, P01CA065493
Status last verified
Nov 2017
First submitted
26 Mar 2014
Last updated
2 Dec 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing T Regulatory cells, Fludarabine and Cyclophosphamide in people with Hematologic Malignancies, 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 33 inclusion and 5 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 phase mean?

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?

Incidence of grade II-IV acute graft-versus-host disease (time frame: Day +100). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02118311.

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.

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