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Genetically Engineered Cells (Anti-CD19/CD20/CD22 CAR T-cells) for the Treatment of Relapsed or Refractory Lymphoid Malignancies

ConditionsRecurrent Acute Lymphoblastic LeukemiaRecurrent B Acute Lymphoblastic LeukemiaRecurrent B-Cell Prolymphocytic LeukemiaRecurrent Chronic Lymphocytic LeukemiaRecurrent High Grade B-Cell LymphomaRecurrent Indolent Non-Hodgkin LymphomaRecurrent Non-Hodgkin LymphomaRecurrent Transformed Chronic Lymphocytic LeukemiaRefractory Acute Lymphoblastic LeukemiaRefractory B Acute Lymphoblastic LeukemiaRefractory B-Cell Prolymphocytic LeukemiaRefractory Chronic Lymphocytic LeukemiaRefractory High Grade B-Cell LymphomaRefractory Indolent Non-Hodgkin LymphomaRefractory Non-Hodgkin LymphomaRefractory Transformed Chronic Lymphocytic LeukemiaRefactory Childhood Acute Lymphoblastic LeukemiaRefractory Childhood Non-Hodgkin Lymphoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2+
SponsorSumithira Vasu

About this trial

This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have come back (recurrent) or do not respond to treatment (refractory). Lymphoid malignancies eligible for this trial are: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-prolymphocytic leukemia (B-PLL). T-cells (a type of white blood cell) form part of the body's immune system. CAR-T is a type of cell therapy that is used with gene-based therapies. CAR T-cells are made by taking a patient's own T-cells and genetically modifying them with a virus so that they are recognized by a group of proteins called CD19/CD20/CD22 which are found on the surface of cancer cells. Anti-CD19/CD20/CD22 CAR T-cells can recognize CD19/CD20/CD22, bind to the cancer cells and kill them. Giving combination chemotherapy helps prepare the body before CAR T-cell therapy. Giving CAR-T after cyclophosphamide and fludarabine may kill more tumor cells.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult subjects with relapsed or refractory non-Hodgkin lymphoma with lesions =< 5 cm, indolent lymphomas, chronic lymphocytic leukemia without Richter's transformation, or B-prolymphocytic leukemia (Cohort A)

OR adult subjects with lymphoid blast crisis, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions > 5 cm and/or lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells, B-Prolymphocytic leukemia with lesions > 5 cm (not including splenomegaly (Cohort B).

OR Pediatric subjects with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

Subjects must have been treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen. B-PLL is defined as having greater than 55% prolymphocytes in the peripheral blood

Disqualifiers

Autologous transplant within 6 weeks of planned CAR-T cell infusion

Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents. Patients with live vaccines given 28 days prior to lymphodepletion (LD) chemotherapy will be excluded

Active graft versus host disease

Active central nervous system or meningeal involvement by lymphoma or leukemia. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration

Trial design

Design model

Parallel

Treatments tested in this trial

  • Anti-CD19/CD20/CD22 CAR T-Cells

    Biological/Vaccine

    Given IV

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine Phosphate

    Drug

    Given IV

  • Echocardiography

    Procedure/Surgery

    Undergo echocardiography

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA scan

  • Biopsy

    Procedure/Surgery

    Undergo tissue biopsy

  • Pheresis

    Procedure/Surgery

    Undergo apheresis

  • Bone Marrow Aspiration and Biopsy

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

Treatment groups

54 Participants
are divided into 3 treatment groups
Group A: Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells)Experimental treatment 9 interventions
Group B: Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)Experimental treatment 9 interventions
Group C: Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

Recommended phase II dose of anti-CD19/CD20/CD22 CAR-T cells for each study group (Cohort A, Cohort B, and Cohort C)

Time frame
Up to 30 days after CAR T-cell infusion

Secondary outcomes

1

Incidence of adverse events

Will be evaluated with descriptive statistics for the frequencies of adverse events of different grades.

Time frame
Up to 12 months after completion of study treatment
2

Overall response rate

Will be evaluated with descriptive statistics with proportions used to describe response rates.

Time frame
Up to 15 years
3

Complete response rate

Will be evaluated with descriptive statistics with proportions used to describe response rates.

Time frame
Up to 15 years
4

Overall survival

Will be calculated using Kaplan Meier method, comparisons between groups will be done using the log rank test.

Time frame
Up to 15 years

Other outcomes

1

Correlation between cytokine serum concentrations and disease response

Will be analyzed with descriptive statistics, including evaluations of median, minimum and peak values. Area under the curve (AUC) will be used as a measure of cytokine secretion. Comparisons will be done between responding and non-responding patients using the Mann - Whitney test for quantitative variables and Fisher's exact test for categorical variables. The Wilcoxon test will be used to evaluate the changes in cytokine concentrations. Correlations between quantitative variables will be done with Spearman's correlation test, whereas correlation between categorical variables will be done using Fisher's exact test.

Time frame
Up to 15 years
2

Presence of measurable CAR-T cells

Will be analyzed with descriptive statistics, including evaluations of median, minimum and peak values. Area under the curve (AUC) will be used as a measure of CAR-T cell expansion and persistence. Comparisons will be done between responding and non-responding patients using the Mann - Whitney test for quantitative variables and Fisher's exact test for categorical variables. The Wilcoxon test will be used to evaluate CAR-T cell expansion and changes in T cell phenotype over time. Correlations between quantitative variables will be done with Spearman's correlation test, whereas correlation between categorical variables will be done using Fisher's exact test.

Time frame
Up to 12 months
3

Correlation between CD19/20/22 expression on disease response

Will be analyzed with descriptive statistics, including evaluations of median, minimum and peak values. Correlations between quantitative variables will be done with Spearman's correlation test, whereas correlation between categorical variables will be done using Fisher's exact test.

Time frame
Up to 15 years

Sponsors and contacts

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

Sumithira Vasu

Lead sponsor

Ohio State University Comprehensive Cancer Center

Sponsor institution

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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