Modified Immune Cells (CD19 CAR T Cells) and Acalabrutinib for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Phase 2

Recruiting

• Conditions: Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma
• Interventions: Drug: Acalabrutinib; Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes

• Registration Number: NCT04484012
• Lead Sponsor: City of Hope Medical Center

Brief Summary

This phase II trial investigates the side effects of CD19 chimeric antigen receptor (CAR) T cells and acalabrutinib, and to see how well they work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize CD19, a protein on the surface of the cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19 positive cancer cells. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CD19 CAR T cells together with acalabrutinib may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate the safety of adding CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes (CD19 CAR T cells) to acalabrutinib treatment. (Safety Lead-in) II. Estimate the complete response (CR) rate within 6 months after adding CD19 CAR T cells to acalabrutinib treatment. (Phase 2)

SECONDARY OBJECTIVES:

I. Assess best response, time to and duration of CR. II. Estimate the 1-year progression free survival (PFS) rate and overall survival (OS).

III. Describe the full toxicity profile.

EXPLORATORY OBJECTIVES:

I. Assess CD19-CAR T cell persistence. II. Assess CD19-CAR T cell activity as measured by CD19 B cell aplasia. III. Describe the duration of CR from completion of acalabrutinib. IV. Describe immunogenicity of CD19-CAR T cells in the presence of the BTK inhibitor.

V. Characterize CD19 expression on tumor cells. VI. Describe cytokine profile after CD19-CAR T cell infusion. VII. Determine BTK and PLCG2 mutational status prior to treatment.

OUTLINE:

Patients receive acalabrutinib orally (PO) twice daily (BID) on days -5 to 28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive CD19 CAR T cells intravenously (IV) on day 0. Treatment with acalabrutinib repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not attained CR after the first disease assessment and tolerated the initial CAR T cell infusion may receive a second CAR T cell infusion in cycle 2.

After completion of study treatment, patients are followed up at 3, 6 and 12 months, then yearly for up to 15 years post CAR T cells infusion.

Study Timeline

• Study First Submitted: 2020-07-07
• Study First Submitted QC: 2020-07-21
• Study First Posted: 2020-07-23
• Study Start: 2020-12-31
• Status Verified: 2024-10
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2024-12-19
• Primary Completion: 2025-09-02
• Study Completion: 2025-09-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (CD19 CAR T cells, acalabrutinib)	CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes	Patients receive acalabrutinib PO BID on days -5 to 28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive CD19 CAR T cells IV on day 0. Treatment with acalabrutinib repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not attained CR after the first disease assessment and tolerated the initial CAR T cell infusion may receive a second CAR T cell infusion in cycle 2.
Treatment (CD19 CAR T cells, acalabrutinib)	Acalabrutinib	Patients receive acalabrutinib PO BID on days -5 to 28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive CD19 CAR T cells IV on day 0. Treatment with acalabrutinib repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not attained CR after the first disease assessment and tolerated the initial CAR T cell infusion may receive a second CAR T cell infusion in cycle 2.

Primary Outcome Measures

Name	Time	Method
Occurrence of dose-limiting toxicities (DLTs) (Safety Lead-in)	Day 0 up to 28 days after the first chimeric antigen receptor (CAR) T cell infusion	Rates and associated 95% Clopper and Pearson exact confidence interval (CI) will be estimated for DLTs at the safe dose.
Complete response (CR) (Phase II)	Within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy	Response will be assessed based on Lugano classification. CR rate is defined as the proportion of response-evaluable participants who achieve a best response of CR within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy. Rates and associated 95% Clopper and Pearson exact CI will be estimated for CR within 6 months.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	From start of protocol treatment (start of lymphodepletion) to death due to any cause, assessed at 1 year	OS will be assessed using Kaplan Meier methods.
Duration of CR	From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years	Duration of CR will be assessed using Kaplan Meier methods.
Time to CR	From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years	Descriptive statistics will be used to summarize the time to CR among those who achieve CR.
Best response	Up to 1 year post CAR T cell infusion	Defined as the best response documented at any time after CAR T cell infusion through 1 year after CAR T cell infusion or the start of any non-protocol anti-lymphoma therapy, whichever occurs first. Best response will be presented in tabular format including counts and percentages.
Progression-free survival (PFS)	From start of protocol treatment (start of lymphodepletion) to the first observation of disease relapse/progression or death due to any cause, whichever occurs first, assessed at 1 year	Progression-free survival will be assessed using Kaplan Meier methods.
Incidence of adverse events	Up to 15 year post CAR T cell infusion	Toxicities will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. Observed toxicities will be summarized by type, severity, date of onset (per each treatment cycle or follow-up period), and attribution.

Trial Locations

Locations (1)

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States