Clinical trial NCT05114837: Ph I/II Study of CAR19 Regulatory T Cells (CAR19-tTreg) for R/R CD19+ B-ALL
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Lymphoma Leukemia
Keywords: CAR19-tTreg
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2021-11-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Evaluate the safety profile and potential efficacy of allogeneic CAR19 regulatory T cells (CAR19-tTreg)
Primary purpose: TREATMENT

Brief 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. The dose finding component is a modified version of a Phase I trial and the extended component is a modified Phase II trial.


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy/immunotherapy, or
  2. First relapse with no CR after 1 cycle of induction therapy, or
  3. Second or greater relapse, or
  4. 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
* Adequate organ function is defined as:

  1. Renal: Calculated estimated glomerular filtration rate greater than or equal to50 mL/min/1.73 m2
  2. 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)
  3. Cardiac: Left ventricular ejection fraction (LVEF) greater than 45% by echocardiogram
  4. 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.

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Dose Finding of CAR19-tTregs
timeFrame: 28 days after CAR19-tTregs administrations
measure: Measure CAR19-tTregs efficacy
timeFrame: 28 days after CAR19-tTregs administrations
Secondary outcomes:
measure: Incidence of CR
timeFrame: 28 days after CAR19-tTregs administrations
measure: Incidence of grade 3-4 cytokine release syndrome (CRS)
timeFrame: 28 days after CAR19-tTregs administrations
measure: Incidence of immune cell associated neurotoxicity syndrome (ICANS)
timeFrame: 28 days after CAR19-tTregs administrations
measure: Incidence of relapse in patients achieving complete response (CR)
timeFrame: 1 year after treatment
measure: Incidence of relapse in patients achieving complete (CR)
timeFrame: Day +100 after treatment
measure: Probability of survival and event free survival
timeFrame: 6 months
measure: Probability of survival and event free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center - University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, Univeristy of Minnesota
name: Bachanova Veronika, MD
role: PRINCIPAL_INVESTIGATOR
References: