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

NCT04484012 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 19405NCI-2020-04550P30CA033572
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Occurrence of dose-limiting toxicities (DLTs) (Safety Lead-in)

  Rates and associated 95% Clopper and Pearson exact confidence interval (CI) will be estimated for DLTs at the safe dose.

  Day 0 up to 28 days after the first chimeric antigen receptor (CAR) T cell infusion

• Complete response (CR) (Phase II)

  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.

  Within 6 months of CAR T-cell infusion and concurrent acalabrutinib therapy

Secondary Outcomes (6)

• 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

• 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

• Best response

  Up to 1 year post CAR T cell infusion

• 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

• Overall survival (OS)

  From start of protocol treatment (start of lymphodepletion) to death due to any cause, assessed at 1 year

Other Outcomes (3)

• CD19 CAR T cell persistence

  At 28 days

• Presence of CD19CAR immunogenicity

  Up to 1 year post CAR T cell infusion

• Duration of CR from completion of acalabrutinib

  Up to 15 years post CAR T cell infusion

Study Arms (1)

Treatment (CD19 CAR T cells, acalabrutinib)

EXPERIMENTAL

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.

Drug: Acalabrutinib; Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Treatment (CD19 CAR T cells, acalabrutinib)

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes BIOLOGICAL

Given IV

Also known as: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ Naive and Memory T Cells, CD19R(EQ)28zetaEGFRt+ Tn/mem Cells

Treatment (CD19 CAR T cells, acalabrutinib)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must have the ability to understand and the willingness to sign a written informed consent.
• Participants must agree to allow the use of archival tissue from diagnostic tumor biopsies.
• If unavailable, exceptions may be granted with Study PI approval. Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed.
• Age Criteria
• Age 18 years and older. Performance Status
• ECOG Performance status ≤ 2 or KPS ≥ 70% (Appendix A) Nature of Illness and Treatment-Related Criteria
• Documented CD19+ MCL by flow cytometry or IHC (from biopsy) if prior CD19 directed therapy was previously used
• a. BM is optional at enrollment IF patient already has biopsy proven disease.
• Participants must be currently receiving acalabrutinib and have been taking acalabrutinib for between 3 and 7 months prior to initiating screening procedures on the study and:
• must have at least 1 prior regimen (not including single-agent corticosteroids)
• best response to acalabrutinib therapy is MRD+ CR, PR or SD at the time of screening b (1) must have measurable disease by CT scan (≥ 1.5 cm) or evidence of blood, spleen, skin, gastrointestinal (GI) or bone marrow involvement Note: Participants who are on other BTK inhibitors, but will thereafter be switched to acalabrutinib prior to lymphodepletion, may be eligible provided that the duration of all BTK inhibitor therapy was ≤ 3-7 months
• No contraindications to leukapheresis, steroids or tocilizumab Clinical Laboratory Criteria (To be performed within 28 days prior to enrollment)
• Total serum bilirubin ≤ 2.0 mg/dL Participants with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
• Blood counts:
• Absolute Neutrophil count (ANC ≥1000 cells/ul)\*

You may not qualify if:

• Allogeneic hematopoietic cell transplantation (HCT) within the last 6 months.
• Autologous HCT within the last 3 months.
• Prior failure of any BTK inhibitor therapy. (Participant WILL be allowed if, after administration of other BTK inhibitors they have switched to acalabrutinib prior to lymphodepletion, and if the duration of all BTK inhibitor therapy was ≤ 3-7 months).
• Participants known to have mutations associated with resistance to BTK inhibitors from prior studies.
• Concomitant therapies
• Approved anti-cancer therapies other than acalabrutinib are not allowed after enrollment, with the exception of steroids or involved field radiation to control progressive disease during cell manufacturing, prior to lymphodepletion/start of protocol therapy.
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
• Unable to discontinue anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of leukapheresis and remain off through end of study treatment.
• Other illnesses or conditions
• Class III/IV cardiovascular disability according to the New York Heart Association Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll.
• Participants with clinically significant arrhythmia or arrhythmias not stable on medical management.
• Active auto-immune disease requiring systemic immunosuppressive therapy, including uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
• Suspected or confirmed progressive multifocal leukoencephalopathy (PML).
• Requires major surgical procedure within 28 days prior to first dose of study drug. If a subject has major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• Participants with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lihua E Budde

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 23, 2020
• Study Start: December 31, 2020
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): September 2, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (1)