LymphomaEarly Phase 1NCT05495464
A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma
A Early Phase 1 study testing Acalabrutinib, Rituximab and Brexucabtagene Autoleucel in people with Lymphoma and Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To learn if giving acalabrutinib, rituximab, and brexucabtagene autoleucel to patients with previously untreated high-risk mantle cell lymphoma (MCL) can help to control the disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Acalabrutinib, Rituximab and Brexucabtagene Autoleucel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Nov 2022to 31 Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of mantle cell lymphoma by hematopathology. MCL should have CD20 positivity (by flow or IHC in tissue or in BM) with presence of chromosome translocation t(11;14), (q13;q32) and/or overexpression of cyclin D1 in tissue biopsy (See Appendix I, footnote 10).
- Newly diagnosed high risk patient without any prior therapy for MCL and are eligible to receive AR and CART cell therapy.
- High risk MCL (Blastoid/pleomorphic histology, high Ki-67 (≥50%), TP53/NOTCH1/2, NSD2, UBR5, FAT1, TRAF2, SP140, POT1, SMARCA4, KMT2D, BIRC3 mutated or any of these mutations or more than 2 mutations with some evidence of prognostic impact, complex karyotype and/or Bulky disease >= 5 cm, FISH positive for TP53 or MYC from involved tissues or TP53 and MYC positive intensity in lymphoma cells in involved tissues (positive by hem-path criteria at MDACC), high risk MIPI score (with Ki-67%). Presence of any or all of these features would qualify as high risk but will need to be reviewed and approved by the study PI. (We will not use any assay which is not FDA approved or not CLIA certified to determine the eligibility of these patients)
- Patients who are eligible to receive CAR T therapy
- Patients who are willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- Understand and voluntarily sign an IRB-approved informed consent form.
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- Age ≥ 18 years at the time of signing the informed consent.
- Bi-dimensional measurable disease using the 2014 Cheson criteria (Measurable disease by PET-CT scan defined as at least 1 lesion that measures ≥ 1.5 cm in single dimension.) Spleen only involved (>=20 cm), these patients are allowed if they meet other high-risk features, determined by the study PI.
- Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less (See Appendix IV).
- An absolute neutrophil count (ANC) > 1,000/mm3 and platelet count >100,000/mm3 (Patients who have >50% bone marrow or spleen infiltration by MCL are eligible if their ANC is ≥ 500/mm3 [growth factor allowed] or their platelet level is equal to or >= than 30,000/mm3. These patients should be discussed with the PI of the study for final approval).
- Serum bilirubin <1.5 mg/dl and Cr Clearance ≥ 60 mL/min by Cockroft-Gault Formula (Appendix VIII) or by >=60 ml/min by 24 hour urine Cr clearance test (Appendix VIII) , AST (SGOT) and ALT (SGPT) < 2.5 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present. Gilbert's disease is allowed.
- Women of childbearing potential (WOBP) must have a negative serum or urine pregnancy test. WOBP and males must be willing to use highly effective methods of birth control. 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 and for 12 months following the last dose of rituximab and 6 months after the completion of CAR T infusion. For male patients with a pregnant or non-pregnant WOCBP partner, should use barrier contraception, during treatment and for 2 days after the last dose of acalabrutinib and for 1 month following the last dose of rituximab and 6 months after the completion of CAR T infusion even if they have had a successful vasectomy. (see Appendix VII).
- Cardiology cleared for receiving acalabrutinib and CART
Who cannot join
- Isolated bone marrow or GI only disease MCL patients and/or lack of measurable disease.
- Pregnant or breast-feeding females.
- Patients who are primary refractory to AR (No response/progressive disease within first 4 months of AR)
- Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
- Known HIV infection.
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- Patients who do not meet high risk features as indicated above. Hepatitis B or C serologic status: 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 polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. 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 to be eligible. Those who are hepatitis C PCR positive will be excluded.
- Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ ca prostate, in situ melanoma (> 5 mm margins) or other cancer from which the subject has been disease free for ≥ 3 years or which will not limit survival to < 3 years.
- Central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML). Magnetic resonance imaging (MRI) of the brain, if performed, showing evidence of central nervous system (CNS) lymphoma or Lumbar puncture with flow cytometry, if performed, with CSF involvement.
- History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
- Active bleeding, history of bleeding diathesis (such as Hemophilia or Von-Willebrand disease), Any history of intracranial bleed or stroke within 6 months of first dose of study drug.
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of acalabrutinib.
- Presence of a clinically significant gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonist, active treatment for pulmonary embolism (PE)/ deep vein thrombosis (DVT) and persons with mechanical cardiac valves.
- History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism requiring systemic anticoagulation within the last 6 months of enrollment
- Concomitant use of corticosteroids at > 20 mg prednisone or equivalent per day longer than 2 weeks.
- Primary immunodeficiency
- History of confirmed autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. Rheumatology clearance required for pts with remote history of auto-immune disease.
- History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
- The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited.
- Requires treatment with strong CYP3A inhibitors or inducers (refer to list in Appendix VI).
- Any of the following cardiac related conditions:
- NYHA Class III and IV heart failure (Appendix IX),
- Active/symptomatic coronary artery disease,
- Myocardial infarction in the preceding 6 months,
- Significant conduction abnormalities, including but not limited to:
- Left bundle branch block,
- 2nd degree AV block type II,
- 3rd degree block,
- QT prolongation (QTc > 500 msec),
- Sick sinus syndrome,
- Ventricular tachycardia,
- Symptomatic bradycardia (heart rate < 50 bpm),
- Persistent and uncontrolled atrial fibrillation.
- Uncontrolled hypertension
- Uncontrolled Hypotension
- Light headedness and syncope,
- Acute infection requiring systemic anti-infective treatment systemic antibiotics, antivirals, or antifungals, or including subjects with positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR] within 14 days prior to initiation of therapy. Patient who exhibit active uncontrolled infection on AR alone will not be excluded but would await adequate infection control and then get CAR T, as long as they have evidence of disease.
- Vaccinated with live, attenuated vaccines within 6 weeks of first dose of study drug.
- Any other serious medical condition including, but not limited to, uncontrolled diabetes mellitus, COPD, renal failure, psychiatric illness or social circumstances that, in the investigator's opinion places the patient at unacceptable risk and would prevent the patient from signing the informed consent form or complying with study procedures.
- Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
- Concurrent participation in another therapeutic clinical trial.
- Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
- Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components.
- Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
Trial locations and contacts
1 site in 1 country.
About this study
To learn if giving acalabrutinib, rituximab, and brexucabtagene autoleucel to patients with previously untreated high-risk mantle cell lymphoma (MCL) can help to control the disease.
Read the detailed description
PRIMARY OBJECTIVES:
To determine the safety profile of the acalabrutinib plus rituximab combination followed by CAR T-cell therapy in newly diagnosed high risk MCL patients.
SECONDARY OBJECTIVES:
To evaluate efficacy measured by complete response (CR) rate and progression free survival (PFS) of the acalabrutinib plus rituximab combination followed by CAR T-cell therapy in newly diagnosed high risk MCL patients.
- Conditions
- Lymphoma, Mantle Cell Lymphoma
- Being tested
- Acalabrutinib, Rituximab, Brexucabtagene Autoleucel, Cyclophosphamide, Fludarabine Phosphate
- Medical subject headings
- Lymphoma, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Given by PO
RituximabDrug
Also called Rituxan
Given by IV (vein)
Brexucabtagene AutoleucelOther
Given by IV (vein)
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
Given by IV (vein)
Also called Fludarabine, Fludara®
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib and Rituximab (Part 1) | Experimental | Participants may receive acalabrutinib and rituximab for up to 12 cycles. Each cycle is 28 days. Receives: Drug: Acalabrutinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate |
| Brexucabtagene Autoleucel (Part 2) | Experimental | Participants will have a procedure called leukapheresis to collect enough T cells. Receives: Other: Brexucabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Unacceptable toxicity is defined as any grade 3 or higher treatment related toxicities happened within 30 days after CAR T-cell infusion. Will monitor the unacceptable toxicity for two patient cohorts together using the Bayesian stopping boundaries calculated based on beta-binomial distribution. The regimen will be considered excessively toxic if the unacceptable toxicity rate at 30 days after CAR T infusion is above 30%. Frequency tables will be used to summarize categorical variables such as toxicity type/severity.
Measured: Within 30 days after CAR T-cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2022
- Study start18 Nov 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Kite, A Gilead Company, Acerta Pharma, LLC
- Responsible party
- Sponsor
- Investigators
- Preetesh Jain, MD, PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05495464
- Sponsor's protocol ID
- 2020-0872
- Other IDs
- NCI-2022-06281
- Status last verified
- Aug 2026
- First submitted
- 28 Jul 2022
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT05495464
- Acronym / sponsor ID
- 2020-0872
- Conditions
- Lymphoma, Mantle Cell Lymphoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Kite, A Gilead Company, Acerta Pharma, LLC
- Study start
- 18 Nov 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 10 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if giving acalabrutinib, rituximab, and brexucabtagene autoleucel to patients with previously untreated high-risk mantle cell lymphoma (MCL) can help to control the disease.
Detailed description
PRIMARY OBJECTIVES:
To determine the safety profile of the acalabrutinib plus rituximab combination followed by CAR T-cell therapy in newly diagnosed high risk MCL patients.
SECONDARY OBJECTIVES:
To evaluate efficacy measured by complete response (CR) rate and progression free survival (PFS) of the acalabrutinib plus rituximab combination followed by CAR T-cell therapy in newly diagnosed high risk MCL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib and Rituximab (Part 1) | Experimental | Drug: Acalabrutinib, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Fludarabine PhosphateParticipants may receive acalabrutinib and rituximab for up to 12 cycles. Each cycle is 28 days. |
| Brexucabtagene Autoleucel (Part 2) | Experimental | Other: Brexucabtagene Autoleucel, Drug: Cyclophosphamide, Drug: Fludarabine PhosphateParticipants will have a procedure called leukapheresis to collect enough T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Confirmed diagnosis of mantle cell lymphoma by hematopathology. MCL should have CD20 positivity (by flow or IHC in tissue or in BM) with presence of chromosome translocation t(11;14), (q13;q32) and/or overexpression of cyclin D1 in tissue biopsy (See Appendix I, footnote 10).
- Newly diagnosed high risk patient without any prior therapy for MCL and are eligible to receive AR and CART cell therapy.
- High risk MCL (Blastoid/pleomorphic histology, high Ki-67 (≥50%), TP53/NOTCH1/2, NSD2, UBR5, FAT1, TRAF2, SP140, POT1, SMARCA4, KMT2D, BIRC3 mutated or any of these mutations or more than 2 mutations with some evidence of prognostic impact, complex karyotype and/or Bulky disease >= 5 cm, FISH positive for TP53 or MYC from involved tissues or TP53 and MYC positive intensity in lymphoma cells in involved tissues (positive by hem-path criteria at MDACC), high risk MIPI score (with Ki-67%). Presence of any or all of these features would qualify as high risk but will need to be reviewed and approved by the study PI. (We will not use any assay which is not FDA approved or not CLIA certified to determine the eligibility of these patients)
- Patients who are eligible to receive CAR T therapy
- Patients who are willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
Key exclusion criteria (47 listed)
- Isolated bone marrow or GI only disease MCL patients and/or lack of measurable disease.
- Pregnant or breast-feeding females.
- Patients who are primary refractory to AR (No response/progressive disease within first 4 months of AR)
- Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibGiven by PO | Drug | Acalabrutinib and Rituximab (Part 1) |
| RituximabAlso: RituxanGiven by IV (vein) | Drug | Acalabrutinib and Rituximab (Part 1) |
| Brexucabtagene AutoleucelGiven by IV (vein) | Other | Brexucabtagene Autoleucel (Part 2) |
| CyclophosphamideAlso: Cytoxan®, Neosar®Given by IV (vein) | Drug | Acalabrutinib and Rituximab (Part 1), Brexucabtagene Autoleucel (Part 2) |
| Fludarabine PhosphateAlso: Fludarabine, Fludara®Given by IV (vein) | Drug | Acalabrutinib and Rituximab (Part 1), Brexucabtagene Autoleucel (Part 2) |
Primary outcome
Incidence of adverse events
Time frame: Within 30 days after CAR T-cell infusion
Unacceptable toxicity is defined as any grade 3 or higher treatment related toxicities happened within 30 days after CAR T-cell infusion. Will monitor the unacceptable toxicity for two patient cohorts together using the Bayesian stopping boundaries calculated based on beta-binomial distribution. The regimen will be considered excessively toxic if the unacceptable toxicity rate at 30 days after CAR T infusion is above 30%. Frequency tables will be used to summarize categorical variables such as toxicity type/severity.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Preetesh Jain, MD, PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Acalabrutinib, Rituximab and Brexucabtagene Autoleucel in people with Lymphoma and Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Within 30 days after CAR T-cell infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.