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CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies

ConditionsRecurrent B-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Small Lymphocytic LymphomaRecurrent Transformed Chronic Lymphocytic LeukemiaRefractory B-Cell Non-Hodgkin LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Small Lymphocytic LymphomaRefractory Transformed Chronic Lymphocytic Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

This phase I trial studies the effects of CD-19 directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with B cell malignancies that have come back (recurrent) or have not responded to treatment (refractory). CD-19 CAR-T cells use some of a patient's own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. Some T cells are removed from the blood, and then laboratory, researchers will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat cancer. The new modified T cells are called the IC19/1563 treatment. IC19/1563 may help treat patients with relapsed/refractory B cell malignancies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >= 18 years

Two or more prior lines of therapy, at least one anthracycline containing regimen, unless intolerable. Exception: Patients with Richter transformation of CLL are eligible if they had >= one prior treatment, including prior BTK inhibition

Demonstration of progressive or stable disease by positron emission tomography/computed tomography (PET/CT) or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma.

Measurable disease defined as measurable by CT portion of a PET/CT: To be considered measurable, the must be at least one lesion that has a single diameter of (>1.5 cm Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy

Disqualifiers

Pregnant persons

Nursing persons

Women of childbearing potential who are unwilling to employ highly effective contraception

Sexually active males who are not willing to use contraception during the study and for >= 12 months after IC19/1563 therapy

Trial design

Design model

Single group

Treatments tested in this trial

  • Autologous Anti-CD19 CAR-expressing T-lymphocytes IC19/1563

    Biological/Vaccine

    Given IV

  • Bendamustine

    Drug

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood and tissue samples

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo CT/PET

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Treatment (cyclophosphamide, fludarabine, IC19/1563)Experimental treatment 10 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose (MTD)

MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

Time frame
90 days

Secondary outcomes

1

Proportion of patients who achieve a successful infusion without manufacturing failure or out of spec products

All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for assessing feasibility. Exact binomial 95% confidence intervals for the true rate of successful infusion will be calculated.

Time frame
Up to 15.5 years
2

Overall response rate (ORR)

ORR will be estimated by the number of patients who achieve a response divided by the total number of evaluable patients who have received a successful chimeric antigen receptor (CAR)-T19 infusion. Response criteria will follow the revised International working group Response Criteria for Malignant Lymphoma or the 2018 International Workshop for Chronic Lymphocytic Leukemia (CLL) response criteria. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

Time frame
From a complete response (CR) or partial response (PR) noted as the objective status at any time after the start of CART19 infusion, assessed up to 15.5 years
3

Duration of response (DOR)

The distribution of duration of response will be estimated using the method of Kaplan Meier.

Time frame
From CR or PR to the date of progression or death, assessed up to 15.5 years
4

Progression-free survival

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

Time frame
From registration to disease progression or death, assessed up to 15.5 years

Other outcomes

1

In vivo cellular kinetics profile of CAR19 cells

The in vivo cellular kinetics profile (levels, persistence, trafficking) of CAR19 transgene and CD3+CAR+ cells into blood will be summarized descriptively. This will include levels of CAR19 transgene by real time polymerase chain reaction in blood and bone marrow and levels of CART19 detected by flow cytometry in blood.

Time frame
Up to 15.5 years
2

Serum/plasma levels of cytokines

Will be monitored at baseline and at multiple time points after CART19 infusion. Values at each time point and changes across time will be summarized graphically and descriptively.

Time frame
Baseline up to 30 days
3

The total number of hospitalizations and ICU admissions

These measures will be summarized descriptively.

Time frame
Up to 15.5 years
4

Length of stay in hospital

These measures will be summarized descriptively.

Time frame
Up to 15.5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov
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