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Lymphoma LeukemiaPhase 1/2NCT05114837

Ph I/II Study of CAR19 Regulatory T Cells (CAR19-tTreg) for R/R CD19+ B-ALL

A Phase 1/2 study testing allogeneic CAR19 regulatory T cells (CAR19-tTreg), Fludarabine and Cyclophosphamide in people with Lymphoma Leukemia, 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Withdrawn

Withdrawn.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 single-center, single-arm, interventional phase I/II trial to evaluate the safety profile and potential efficacy of allogeneic CAR19 regulatory T cells (CAR19-tTreg) in adults with relapsed/refractory (R/R) CD19+ B Acute Lymphocytic Leukemia (B-ALL). The study consists of two components. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma Leukemia
What is being tested?
allogeneic CAR19 regulatory T cells (CAR19-tTreg), Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Sep 2024to Aug 2028
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of R/R CD19+ B-ALL after failure of standard of care therapies with CD19 expression on blasts confirmed by flow cytometry or immunohistochemistry and meeting one or more of the following criteria:
  • Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy/immunotherapy, or
  • First relapse with no CR after 1 cycle of induction therapy, or
  • Second or greater relapse, or
  • Ph+ ALL and failure or intolerance to three lines of tyrosine kinase inhibitors (TKI) assuming one or more of the above criteria are also met.
  • Karnofsky performance status (KPS) ≥70% at screening
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  • Adequate organ function is defined as:
  • Renal: Calculated estimated glomerular filtration rate greater than or equal to50 mL/min/1.73 m2
  • Hepatic: ALT and AST less than 3x upper limit of normal (ULN), and bilirubin less than2x ULN (exception, patients with Gilbert syndrome, total less than 3 x ULN and direct less than 1.5 x ULN)
  • Cardiac: Left ventricular ejection fraction (LVEF) greater than 45% by echocardiogram
  • Pulmonary: SpO2 greater than 92% on room air
  • Use of antiproliferative chemotherapy more than 2 weeks prior to enrollment and blinatumomab more than 4 weeks prior to enrollment
  • Patients with relapsed disease after prior allogeneic transplantation may be considered. In addition to the eligibility criteria otherwise listed, this subgroup must be more than 3 months from allogeneic hematopoietic stem cell transplant (HSCT), off immune suppressive therapy (e.g., calcineurin inhibitor, glucocorticoid, sirolimus) at least 4 weeks without GVHD.
  • Patients who received prior CAR-T therapy are eligible if more than 2 months after CAR-T infusion and CD19 expression is confirmed at the most recent relapse and all other criteria are met
  • Voluntary informed consent by the patient for treatment and follow-up for 15 years after treatment.

Who cannot join

  • Availability of a FDA approved CAR T cell therapeutic targeting CD19+ B-ALL (patients eligible for but unable to receive FDA approved CAR T cells based on insurance limitations, may be eligible for the proposed trial)
  • Use of pharmacological immunosuppressive agents within 2 weeks (with the exception of physiologic or stress dose glucocorticoid replacement) or anti-T cell antibodies within 2 months of study participation
  • Diagnosis of Burkitt lymphoma
  • Diagnosis of active central nervous system (CNS) leukemia
  • Known allergy to manufacturing components: human albumin or dimethylsulfoxide (DMSO)
  • History of HIV infection on anti-retroviral therapy
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  • Positive for hepatitis B or hepatitis C
  • Active uncontrolled bacterial, fungal, or viral infections - all prior infections must have resolved or be improving following optimal therapy
  • Active autoimmune disease requiring immunosuppressive therapy
  • Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, or supraventricular tachyarrhythmia requiring chronic therapy)
  • Females who are pregnant or breastfeeding
  • Unstable angina, arrhythmias, evidence of acute ischemia or conduction system abnormalities by electrocardiogram (ECG) or myocardial infarction in prior to 2 months
  • Use of other investigational agents within 2 weeks

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center - University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Phase I/II First-in-Human Trial With CAR19 Regulatory T Cells (CAR19-tTreg) in Adults With Relapsed/Refractory CD19+ B Acute Lymphocytic Leukemia

This is a single-center, single-arm, interventional phase I/II trial to evaluate the safety profile and potential efficacy of allogeneic CAR19 regulatory T cells (CAR19-tTreg) in adults with relapsed/refractory (R/R) CD19+ B Acute Lymphocytic Leukemia (B-ALL).

The study consists of two components. The dose finding component is a modified version of a Phase I trial and the extended component is a modified Phase II trial.

Being tested
allogeneic CAR19 regulatory T cells (CAR19-tTreg), Fludarabine, Cyclophosphamide
Keywords
CAR19-tTreg

What participants receive

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

  • allogeneic CAR19 regulatory T cells (CAR19-tTreg)Drug

    A single dose administration of CAR19-tTreg

  • FludarabineDrug

    Also called FLUDARA

    Fludarabine 30 mg/m^2 is administered as an intravenous (IV) infusion per institutional guidelines once a day on 4 consecutive days (Day -5, Day -4, Day -3 and Day -2)

  • CyclophosphamideDrug

    Also called CYTOXAN

    Cyclophosphamide 500 mg/m^2 is administered as an IV infusion per institutional guidelines once a day on 2 consecutive days (Day -5, and Day -4)

Study groups in NCT05114837
Study groupRoleWhat they receive
Phase I/IIExperimentalDetermine the maximum tolerated dose (MTD) of CAR19-tTreg. It will be administered in a single dose after high dose lymphodepleting chemotherapy to promote adoptive transfer. First dose of 1.0 x 10 6 CAR19-tTreg/kg recipient body weight (dose level 1).The subsequent doses are 3.0, 10.0 and 30.0 x 10 6 CAR19- tTreg/kg. PHASE II Expand trial on maximum tolerated dose (MTD) of CAR19-tTreg from Phase I. It will be administered in a single dose after high dose lymphodepleting chemotherapy to promote adoptive transfer.The CAR19-tTreg/kg dose is to be determined.
Receives: Drug: allogeneic CAR19 regulatory T cells (CAR19-tTreg); Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Dose Finding of CAR19-tTregs

    To identify the MTD of CAR19-tTregs defined asthe dose level that most closely corresponds to a dose limiting toxicity rate(DLT) less than or equal to 25%. Using grade 3-5 Common Terminology Criteria for Adverse Events version 5 (CTCAEv5) Statistical Analysis: The proportion of patients with ORR, CR and adverse events by day 28 will be estimated by simple proportions with 95% confidence intervals

    Measured: 28 days after CAR19-tTregs administrations

  2. Measure CAR19-tTregs efficacy

    Efficacy estimate as measured by overall response rate

    Measured: 28 days after CAR19-tTregs administrations

Secondary outcomes (7)

  1. Incidence of CR

    Report number patients that achieved complete response (CR)

    Measured: 28 days after CAR19-tTregs administrations

  2. Incidence of grade 3-4 cytokine release syndrome (CRS)

    Evaluated using the American Society of Transplantation and Cellular Therapy (ASTCT) CRS consensus grading system

    Measured: 28 days after CAR19-tTregs administrations

  3. Incidence of immune cell associated neurotoxicity syndrome (ICANS)

    Report the count of neurotoxicities based on the ICANS system.

    Measured: 28 days after CAR19-tTregs administrations

  4. Incidence of relapse in patients achieving complete response (CR)

    Report the count of relapses out of those that achieved complete reponse

    Measured: 1 year after treatment

  5. Incidence of relapse in patients achieving complete (CR)

    Report the count (as proportions) of relapses out of those that achieved complete re

    Measured: Day +100 after treatment

  6. Probability of survival and event free survival

    The analysis of overall survival will use death as the event, and the analysis of event-free survival will use the earliest of no response, relapse, or death as the event. Patients who do not have an event will have their data censored for the analyses at the date at which they were last known to be alive. Finally, probabilities will be measured using Kaplan-Meier curves

    Measured: 6 months

  7. Probability of survival and event free survival

    The analysis of overall survival will use death as the event, and the analysis of event-free survival will use the earliest of no response, relapse, or death as the event. Patients who do not have an event will have their data censored for the analyses at the date at which they were last known to be alive. Finally, probabilities will be measured using Kaplan-Meier curves

    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 posted10 Nov 2021
  2. Study startSep 2024 (estimated)
  3. Primary completionAug 2028 (estimated)
  4. Study completionAug 2028 (estimated)

Why it stopped: replaced with a new IND and 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Evaluate the safety profile and potential efficacy of allogeneic CAR19 regulatory T cells (CAR19-tTreg)
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05114837
Sponsor's protocol ID
2021LS012
Other IDs
MT2021-02
Status last verified
Jul 2024
First submitted
29 Oct 2021
Last updated
19 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing allogeneic CAR19 regulatory T cells (CAR19-tTreg), Fludarabine and Cyclophosphamide in people with Lymphoma 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 15 inclusion and 13 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 19 Jul 2024. 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?

Dose Finding of CAR19-tTregs (time frame: 28 days after CAR19-tTregs administrations). The study lists 2 primary outcomes in all. 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 NCT05114837.

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 19 Jul 2024.

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