AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 2NCT02991898

Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies

A Phase 2 study testing Infusion of Treg in people with Acute Lymphoblastic Leukemia and Burkitt Lymphoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a single center pilot study of a non-myeloablative umbilical cord blood transplant for the treatment of a hematological malignancy with a single infusion of T regulatory (Treg) given shortly after UCB transplantation. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Infusion of Treg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
16 Feb 2017to 20 Jun 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 75 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 7/8 or 8/8 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)
  • UCB unit(s) composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm and an additional cord blood unit to be used as the source to manufacture the Treg product. This UCB unit must be matched at 4-6/6 to the patient, considering HLA-A, B at the antigen level and DRB1 at the allele level
  • Acute Leukemias: Must be in remission by morphology. 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. Refer to Section 5.2 for complete definitions.
  • Burkitt's Lymphoma in CR2 or subsequent CR
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia: all types except refractory blast crisis. Chronic phase patients must have failed at least two different tyrosine-kinase inhibitors (TKIs), or been intolerant to all available TKIs or have T315I mutation.
Show all 21Show fewer
  • Myelodysplastic Syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be be < 5%, preferably < 20% blasts by morphology by bone marrow aspirate morphology.. If ≥ 5% blasts, chemotherapy for cytoreduction to <5% blasts prior to transplantation may be considered.
  • Chronic myeloid neoplasms, including but not limited to CMML with blasts must around 5% blasts, preferably < 20% blasts by morphology by bone marrow aspirate morphology. If ≥5% blasts, chemotherapy for cytoreduction to <5% blasts prior to transplantation may be considered.
  • 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 transplant on this study or have received multi-agent or immunosuppressive chemotherapy within 3 months of the preparative regimen.
  • Performance Status, Organ Function, Contraception Use
  • Karnofsky score ≥ 70% (Appendix II)
  • Adequate organ function within 14 days (30 days for cardiac and pulmonary) of registration on-study 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
  • ALT, AST and alkaline phosphatase ≤ 5 x upper limit of normal and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
  • Pulmonary function: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements.
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%.
  • Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
  • Voluntary written consent

Who cannot join

  • Untreated active infection
  • 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 (if applicable)
  • Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
Show all 9Show fewer
  • CML in blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
  • Active central nervous system malignancy

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Adoptive Transfer of T Regulatory Cell for Suppression of Acute Graft-vs-Host-Disease After an Umbilical Cord Blood Transplant for Hematologic Malignancies

This is a single center pilot study of a non-myeloablative umbilical cord blood transplant for the treatment of a hematological malignancy with a single infusion of T regulatory (Treg) given shortly after UCB transplantation.

Being tested
Infusion of Treg
Keywords
CML, MDS, CLL, ALL, AML
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Dendritic Cell Sarcoma, Interdigitating, 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.

  • Infusion of TregBiological

    Also called T regulatory cells

    Allopurinol on day -7 to day 0 Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 Fludarabine 30mg/m2 IV over 1 hour on day -6, -5, -4, -3, and -2 Total Body Irradiation 200 cGy as a single dose

    Sirolimus 8mg-12mg oral loading dose followed by single dose 4mg/day. Levels are to be monitored 3 times/week in the first week, weekly until day +60, and as clinically indicated until day +100 post-transplantation.

    Mycophenolate Mofetil (MMF) 3 gram/day IV/PO divided in 2 or 3 doses. Stop MMF at day +30 or 7 days after neutrophil recovery, whichever day is later, if no acute GVHD.

    DUCBT followed Tregs - double umbilical cord blood transplant (FIRST) followed by the Treg cell infusion (SECOND) no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion.

Study groups in NCT02991898
Study groupRoleWhat they receive
Treg InfusionExperimentalThe Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion
Receives: Biological: Infusion of Treg

What is being measured

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

  1. Number of Participants Survived

    Count of patients who survived 2 years post intervention

    Measured: 2 years

Secondary outcomes (13)
  1. Number of Participants With Grade II-IV aGVHD

    Probability of grade II-IV aGVHD

    Measured: Assessed weekly until day 100, then day 180, 360

  2. Number of Participants Experiencing Treatment Related Mortality (TRM)

    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.

    Measured: 6 months

  3. Number of Participants Who Experienced Relapse

    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.

    Measured: 1 year

  4. Number of Participants With Incidence of Bacterial, Viral and Fungal Infections

    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.

    Measured: 1 year

  5. Number of Participant With Detectable Treg Cells at d14

    The proportion of patients with detectable Treg cells at day 14 post infusion

    Measured: 14 days

  6. Number of Participants With Immune Reconstitution

    The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.

    Measured: Assessed at Day 4, weekly for 8 weeks

  7. Number of Participants Experiencing Treg Cell Infusion Toxicity

    Incidence of Adverse Events

    Measured: 48 hours post infusion

  8. Length of Treg Survival

    Length of Treg survival after infusion of Treg.

    Measured: 24 hours post infusion

  9. Percentage of Donor Cell Chimerism

    The incidence of chimerism in patients treated

    Measured: Day +100

  10. Number of Participants Survived One Year Post-transplant

    The probability of survival, one year post-treatment

    Measured: 1 year

  11. Number of Participants With Neutrophil Recovery

    The incidence of neutrophil recovery, that is return of neutrophil counts to ≥ 5 X 10^8/L in treated patients

    Measured: Day 42

  12. Number of Participants With Platelet Recovery

    The incidence of platelet recovery (return of platelet counts to > 20,000/μL) in treated patients

    Measured: 1 year

  13. Number of Participants With Chronic GVHD

    The incidence of chronic GVHD in treated patients after one 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.

  1. First posted14 Dec 2016 (estimated)
  2. Study start16 Feb 2017
  3. Primary completion20 Jun 2019
  4. Study completion20 Jun 2019

Why it stopped: Considering new technology for product.

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02991898
Sponsor's protocol ID
2016LS107
Other IDs
MT2016-17
Status last verified
Sep 2020
First submitted
7 Dec 2016
Last updated
29 Sep 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Infusion of Treg in people with Acute Lymphoblastic Leukemia and Burkitt Lymphoma, 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 21 inclusion and 9 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: stopped early, as of the sponsor's last update on 29 Sep 2020. 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?

Yes. Results are posted in the registry (first posted 24 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Survived (time frame: 2 years). 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 29 Sep 2020.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in