Blastoid Variant Mantle Cell LymphomaPhase 2NCT03946878
Venetoclax and Acalabrutinib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
A Phase 2 study testing Acalabrutinib and Venetoclax in people with Blastoid Variant Mantle Cell Lymphoma and CCND1 Protein Overexpression, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well venetoclax and acalabrutinib work in treating patients with mantle cell lymphoma that did not respond to previous treatment or has come back. Venetoclax may cause cancer cell death by blocking the mechanism that cancer cells use to stay alive. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blastoid Variant Mantle Cell Lymphoma, CCND1 Protein Overexpression, CD20 Positive
- What is being tested?
- Acalabrutinib and Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2019to 8 Feb 2028
- Phase
- Phase 2
- 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 MCL in previously treated relapsed/refractory patients with/without chromosome translocation t(11;14), (q13;q32) by FISH and/or overexpress cyclin D1 in tissue biopsy (blastoid/pleomorphic morphology, complex karyotype is acceptable), cyclin D1 negative mantle cell lymphoma is allowed. MCL diagnosis confirmation is needed by pathologist.
- Disease had relapsed after or been refractory to >= 1 prior therapy for MCL and now requires further treatment.
- Ability to understand the purpose and risks of the study and provide signed and dated Institutional Review Board (IRB) approved informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
- Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- Age ≥ 18 years at the time of signing the ICF.
- Bi-dimensional measurable disease using the Cheson criteria (measurable disease by computed tomography [CT] scan defined as at least 1 lesion that measures >= 1.5 cm in single dimension). Gastrointestinal (GI), bone marrow or spleen only patients are allowable.
Show all 18Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. The following laboratory criteria must be met
- Absolute neutrophil count (ANC) > 1,000/mm^3 independent of growth factor support.
- Platelet count >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involved with lymphoma, independent of transfusion support in either situation.
- Creatinine (Cr) =< 2 or Cr clearance >= 30 mL/min.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN), serum bilirubin < 1.5 mg/dl, unless due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin.
- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN and partial thromboplastin time (PTT) =< 1.5 x ULN.
- Disease free of prior malignancies other than MCL with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated with life expectancy of > 3 years. Principal investigator (PI) can use clinical judgement in the best interest of patients.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and willing to use highly effective methods of birth control.
- Male subjects must agree to refrain from sperm donation during the study.
- A female of childbearing potential is a sexually mature woman who:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
Who cannot join
- Prior treatment with acalabrutinib or any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
- Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
- Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment.
- Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease, renal failure, active hemorrhage, or psychiatric illness that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the ICF.
- Pregnant or breast-feeding females.
Show all 21Show fewer
- Known human immunodeficiency virus (HIV) infection.
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP). History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
- Any active significant infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR]).
- Serologic status reflecting active hepatitis B or C infection.
- a. 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 randomization 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. b. Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
- Central nervous system (CNS) disease with serious significance.
- Refractory nausea and vomiting, inability to swallow the formulated product, or Malabsorption syndrome, disease significantly affecting GI 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 GI condition that could interfere with the absorption metabolism, and excretion of acalabrutinib or venetoclax.
- Major surgical procedure within 30 days before the 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.
- Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to study entry
- Requires anticoagulation with warfarin or equivalent vitamin K antagonist
- Vaccinated with live, attenuated vaccines within 4 weeks of study entry
- Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration of >10mg/day of prednisone or equivalent) within 28 days of the first dose of study drug.
- Requires treatment with strong CYP3A inhibitors or inducers or strong CYP1A2 inhibitors (refer to list in Appendix V and Sections 8.2.1 and 8.2.2).
- Refractory to prior ibrutinib or BTK mutation or previous exposure to other BTK inhibitors
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, Phase II Investigator Initiated Study of Venetoclax and Acalabrutinib in Previously Treated Relapsed/Refractory Patients With Mantle Cell Lymphoma (MCL)
This phase II trial studies how well venetoclax and acalabrutinib work in treating patients with mantle cell lymphoma that did not respond to previous treatment or has come back. Venetoclax may cause cancer cell death by blocking the mechanism that cancer cells use to stay alive. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and acalabrutinib together may kill more cancer cells in patients with mantle cell lymphoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of a combination of venetoclax and acalabrutinib, in patients with previously treated relapsed/refractory mantle cell lymphoma (MCL).
SECONDARY OBJECTIVES:
- To evaluate the efficacy of this combination regimen in previously treated subjects with relapsed/refractory MCL with overall response rate (ORR), duration of response (DOR), event free survival (EFS), progression free survival (PFS), and overall survival (OS).
II. To evaluate the safety and tolerability of venetoclax and acalabrutinib in previously treated subjects with relapsed/refractory MCL.
CORRELATIVE/TRANSLATIONAL COMPONENT OBJECTIVES:
- Sequential peripheral blood (PB)/plasma/tissue fine needle aspirate will be stored.
II. Clonal evolution with targeted sequencing (seq) and/or whole exome sequencing (WES) in sequential samples.
III. Pattern of mutation changes with Bruton tyrosine kinase inhibitor (BTKi) or with venetoclax resistance.
IV. Response predictors - mutations, cytokine-chemokines, clonal evolution (CE).
- Minimal residual disease (MRD) assay using circulating tumor deoxyribonucleic acid (ctDNA) analysis, flow cytometry at various time points from peripheral blood (PB)/ bone marrow (BM).
VI. Sequential immunologic studies with cytokines/chemokines, T cell numbers, and immunoglobulins (Ig).
VII. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib - venetoclax (A-V) treatment.
OUTLINE: This is a dose escalation study of venetoclax.
Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, then every 4 months for 2 years, then every 6 months for the next 2 years, and then annually thereafter.
- Conditions
- Blastoid Variant Mantle Cell Lymphoma, CCND1 Protein Overexpression, CD20 Positive, CD5 Positive, FCER2 Negative, Pleomorphic Variant Mantle Cell Lymphoma
- Being tested
- Acalabrutinib, Venetoclax
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (acalabrutinib, venetoclax) | Experimental | Patients receive acalabrutinib PO BID on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Acalabrutinib; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR)
Assessed by Lugano criteria - positron emission tomography (PET)-computed tomography, and in a subset of patients by bone marrow flow cytometry, circulating tumor deoxyribonucleic acid and endoscopy if at baseline there is gut involvement. Response will be calculated separately with and without knowledge of the PET result by International Working Group criteria, in order to provide context in relation to historical control data. Will estimate the CR along with the 95% credible interval.
Measured: 16 weeks
Secondary outcomes (6)
Overall response rate
Measured: 5 years
Duration of response
Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: 5 years
Event free survival
Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: 5 years
Progression free survival
Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: 5 years
Overall survival
Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: 5 years
Incidence of adverse events
Safety data will be summarized by frequency tables for all patients. Per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start13 Aug 2019
- Primary completion8 Feb 2028 (estimated)
- Study completion8 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blastoid Variant Mantle Cell 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Luhua (Michael) Wang, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03946878
- Sponsor's protocol ID
- 2018-0935
- Other IDs
- NCI-2019-02354, 2018-0935
- Status last verified
- Aug 2026
- First submitted
- 9 May 2019
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase II Investigator Initiated Study of Venetoclax and Acalabrutinib in Previously Treated Relapsed/Refractory Patients With Mantle Cell Lymphoma (MCL)
- ClinicalTrials.gov ID
- NCT03946878
- Acronym / sponsor ID
- 2018-0935
- Conditions
- Blastoid Variant Mantle Cell Lymphoma, CCND1 Protein Overexpression, CD20 Positive, CD5 Positive, FCER2 Negative, Pleomorphic Variant Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Aug 2019 (actual)
- Primary completion
- 8 Feb 2028 (estimated)
- Study completion
- 8 Feb 2028 (estimated)
- First posted
- 13 May 2019 (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.
This phase II trial studies how well venetoclax and acalabrutinib work in treating patients with mantle cell lymphoma that did not respond to previous treatment or has come back. Venetoclax may cause cancer cell death by blocking the mechanism that cancer cells use to stay alive. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and acalabrutinib together may kill more cancer cells in patients with mantle cell lymphoma.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of a combination of venetoclax and acalabrutinib, in patients with previously treated relapsed/refractory mantle cell lymphoma (MCL).
SECONDARY OBJECTIVES:
- To evaluate the efficacy of this combination regimen in previously treated subjects with relapsed/refractory MCL with overall response rate (ORR), duration of response (DOR), event free survival (EFS), progression free survival (PFS), and overall survival (OS).
II. To evaluate the safety and tolerability of venetoclax and acalabrutinib in previously treated subjects with relapsed/refractory MCL.
CORRELATIVE/TRANSLATIONAL COMPONENT OBJECTIVES:
- Sequential peripheral blood (PB)/plasma/tissue fine needle aspirate will be stored.
II. Clonal evolution with targeted sequencing (seq) and/or whole exome sequencing (WES) in sequential samples.
III. Pattern of mutation changes with Bruton tyrosine kinase inhibitor (BTKi) or with venetoclax resistance.
IV. Response predictors - mutations, cytokine-chemokines, clonal evolution (CE).
- Minimal residual disease (MRD) assay using circulating tumor deoxyribonucleic acid (ctDNA) analysis, flow cytometry at various time points from peripheral blood (PB)/ bone marrow (BM).
VI. Sequential immunologic studies with cytokines/chemokines, T cell numbers, and immunoglobulins (Ig).
VII. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib - venetoclax (A-V) treatment.
OUTLINE: This is a dose escalation study of venetoclax.
Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, then every 4 months for 2 years, then every 6 months for the next 2 years, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (acalabrutinib, venetoclax) | Experimental | Drug: Acalabrutinib, Drug: VenetoclaxPatients receive acalabrutinib PO BID on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Confirmed diagnosis of MCL in previously treated relapsed/refractory patients with/without chromosome translocation t(11;14), (q13;q32) by FISH and/or overexpress cyclin D1 in tissue biopsy (blastoid/pleomorphic morphology, complex karyotype is acceptable), cyclin D1 negative mantle cell lymphoma is allowed. MCL diagnosis confirmation is needed by pathologist.
- Disease had relapsed after or been refractory to >= 1 prior therapy for MCL and now requires further treatment.
- Ability to understand the purpose and risks of the study and provide signed and dated Institutional Review Board (IRB) approved informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
- Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- Age ≥ 18 years at the time of signing the ICF.
Key exclusion criteria (21 listed)
- Prior treatment with acalabrutinib or any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
- Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease, renal failure, active hemorrhage, or psychiatric illness that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the ICF.
- Pregnant or breast-feeding females.
- Known human immunodeficiency virus (HIV) infection.
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 |
|---|---|---|
| AcalabrutinibAlso: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, CalquenceGiven PO | Drug | Treatment (acalabrutinib, venetoclax) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (acalabrutinib, venetoclax) |
Primary outcome
Complete response (CR)
Time frame: 16 weeks
Assessed by Lugano criteria - positron emission tomography (PET)-computed tomography, and in a subset of patients by bone marrow flow cytometry, circulating tumor deoxyribonucleic acid and endoscopy if at baseline there is gut involvement. Response will be calculated separately with and without knowledge of the PET result by International Working Group criteria, in order to provide context in relation to historical control data. Will estimate the CR along with the 95% credible interval.
6 secondary outcomes
Overall response rate
Time frame: 5 years
Duration of response
Time frame: 5 years
Event free survival
Time frame: 5 years
Progression free survival
Time frame: 5 years
Overall survival
Time frame: 5 years
Incidence of adverse events
Time frame: 5 years
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 10 Aug 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
Related trials for Blastoid Variant Mantle Cell Lymphoma
RecruitingPhase 1/2
Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma
Blastoid Variant Mantle Cell Lymphoma, Mantle Cell Lymphoma
Active, not recruitingPhase 2
Ibrutinib, Rituximab, and Consolidation Chemotherapy in Treating Young Patients With Newly Diagnosed Mantle Cell Lymphoma
Blastoid Variant Mantle Cell Lymphoma, Mantle Cell Lymphoma
Not yet recruitingPhase 2
Linperlisib Plus Obinutuzumab and Venetoclax for Relapsed and Refractory Blastoid Variant of Mantle Cell Lymphoma.
Mantle Cell Lymphoma
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.
Luhua (Michael) Wang 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 Phase 2 study testing Acalabrutinib and Venetoclax in people with Blastoid Variant Mantle Cell Lymphoma and CCND1 Protein Overexpression, 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 18 inclusion and 21 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 10 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Complete response (CR) (time frame: 16 weeks). 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 10 Aug 2026.