Acalabrutinib + Liso-Cel In R/R Aggressive B-Cell Lymphomas

NCT05583149 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 21-422
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to assess the effectiveness and safety of acalabrutinib combined with lisocabtagene maraleucel (liso-cel) for people with relapsed/refractory aggressive B-cell lymphoma. This research study involves the study drug acalabrutinib in combination with lisocabtagene maraleuce

Conditions

Refractory Aggressive B-cell Lymphomas; Refractory B-Cell Non-Hodgkin Lymphoma; Aggressive B-cell NHL; Diffuse Large B-cell Lymphoma (DLBCL); De Novo or Transformed Indolent B-cell Lymphoma; DLBCL, Nos Genetic Subtypes; T Cell/Histiocyte-rich Large B-cell Lymphoma; EBV-Positive DLBCL, Nos; Primary Mediastinal [Thymic] Large B-cell Lymphoma (PMBCL); High-Grade B-Cell Lymphoma, Nos; C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma; Grade 3b Follicular Lymphoma; C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma

Keywords

Refractory aggressive B-cell lymphomas; Refractory B-Cell Non-Hodgkin Lymphoma; Aggressive B-cell NHL; Diffuse Large B-cell Lymphoma (DLBCL); De novo or transformed indolent B-cell lymphoma; DLBCL, nos Genetic Subtypes; T cell/histiocyte-rich large B-cell lymphoma; EBV-Positive DLBCL, nos; Primary mediastinal [thymic] large B-cell lymphoma (PMBCL); High-Grade B-Cell Lymphoma, nos; C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma; Grade 3b Follicular Lymphoma; C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  The CRR is defined as the percentage of subjects achieving an objective response of complete response (CR) according to the Lugano Classification (Chesson et al., 2014), prior to start of another non-study anticancer therapy. CR is defined as a complete metabolic and radiologic response (Lugano score 1-3, target nodes/nodal masses must regress to ≤ 1.5 cm in longest diameter.)

  1 year 8 months

Secondary Outcomes (15)

• Overall Response Rate

  3 Months

• Overall Response Rate

  6 Months

• Overall Response Rate

  12 Months

• Progression Free Survival

  as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation up to 15 years

• Overall Survival

  defined as the time from registration to death due to any cause, or censored at date last known alive up to 15 years

Study Arms (1)

ACALABRUTINIB and LISOCABTAGENE MARALEUCEL

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, as tolerated for one year * Liso-cel * Acalabrutinib

Drug: ACALABRUTINIB; Drug: LISOCABTAGENE MARALEUCEL; Drug: Lymphodepleting chemotherapy

Interventions

ACALABRUTINIB DRUG

Oral, twice daily, timing and dosage per protocol

Also known as: Calquence

ACALABRUTINIB and LISOCABTAGENE MARALEUCEL

LISOCABTAGENE MARALEUCEL DRUG

via IV timings and dosage per protocol

Also known as: Breyanzi

ACALABRUTINIB and LISOCABTAGENE MARALEUCEL

Lymphodepleting chemotherapy DRUG

lymphodepleting chemotherapy with cyclophosphamide and fludarabine once a day for 3 days via IV about 2-4 hours. This will occur only once prior to lisocabtagene maraleucel infusion.

Also known as: cyclophosphamide and fludarabine

ACALABRUTINIB and LISOCABTAGENE MARALEUCEL

Eligibility Criteria

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

You may qualify if:

• Adult patients ≥18 years with histologically confirmed aggressive B-cell NHL including diffuse large B-cell lymphoma (DLBCL), either de novo or transformed from any indolent B-cell lymphoma, and including DLBCL NOS, T cell/histiocyte-rich large B-cell lymphoma, Epstein-Barr virus \[EBV\] positive DLBCL NOS, primary mediastinal \[thymic\] large B-cell lymphoma (PMBCL), high grade B-cell lymphoma NOS, or high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements \[double/triple hit lymphoma (DHL/THL)\]; and grade 3B follicular lymphoma. Patients with primary CNS lymphoma are not eligible. Patients with secondary CNS involvement by lymphoma are eligible if they otherwise meet all eligibility criteria.
• Relapsed or refractory to at least 2 prior lines of systemic lymphoma therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline or alkylating agent.
• PET-positive measurable disease
• ECOG Performance status 0-2
• Estimated creatinine clearance of ≥30 mL/min, calculated using the Cockcroft and Gault equation (if male, \[140Age\] x Mass \[kg\] / \[72 x creatinine g/dL\];multiply by 0.85 if female)
• Alanine Aminotransferase (ALT) \<= 2.5 times the ULN
• Bilirubin \<= 2 x ULN (or \<= 3.0 mg/dL for patients with Gilbert-Meulengracht syndrome or lymphomatous involvement of the liver)
• Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) \>= 40% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)
• For subjects with atrial fibrillation, atrial fibrillation must be controlled and asymptomatic
• Absolute neutrophil count (ANC) \>= 1000/mm3
• Platelets \>= 50,000/mm3
• Adequate pulmonary function, defined as \<= CTCAE Grade 1 dyspnea and SaO2 \> 91% on room air
• Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)
• Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib.
• Willing and able to participate in all required evaluations and procedures in this study protocol.

You may not qualify if:

• Another active malignancy which requires concurrent cancer-directed therapy
• Previous treatment with gene therapy product or adoptive T cell therapy
• Allogeneic stem cell transplant within 90 days of leukapheresis
• Active acute or chronic GVHD
• HIV infection
• Serologic status reflecting active hepatitis B or C infection
• Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before enrollment and must be willing to undergo DNA PCR testing during the study. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded.
• Subjects who are hepatitis C antibody positive will need to have a negative PCR result before enrollment. Those who are hepatitis C PCR positive will be excluded.
• Uncontrolled infection
• Clinically relevant CNS pathology
• History of cardiovascular conditions within the past 6 months, including class III or IV heart failure as defined by New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or clinically significant arrhythmias: Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Autoimmune disease requiring chronic systemic corticosteroids at a dose of greater than 10 mg of prednisone daily or an equivalent dose of another corticosteroid
• Treatment with alemtuzumab within 6 months leukapheresis or fludarabine or cladribine within 3 months of leukapheresis
• Therapeutic anticoagulation
• Bleeding diathesis

Sponsors & Collaborators

• Patrick C. Johnson, MD: lead
• AstraZeneca: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Beth-Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Pyloric Stenosis, Hypertrophic

Interventions

acalabrutinib; Cyclophosphamide; fludarabine

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; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Patrick Connor Johnson, MD
• Organization: Massachusetts General Hospital

pcjohnson@mgh.harvard.edu

6177244000

Study Officials

• Connor Johnson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 17, 2022
• Study Start: March 1, 2023
• Primary Completion: November 23, 2024
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)