Mantle Cell LymphomaPhase 2NCT05025423
Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma
A Phase 2 study testing Venetoclax Oral Tablet [Venclexta] in people with Mantle Cell Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
The proposed study is an open-label, single arm phase II study of venetoclax in combination with rituximab in patients over the age of 60 with previously untreated mantle cell lymphoma. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Venetoclax Oral Tablet [Venclexta]
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2022to 14 May 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma as defined by the World Health Organization (WHO) classification scheme.
- Age ≥ 60
- Subjects must be previously untreated for mantle cell lymphoma and deemed to require treatment by the treating physician
- ECOG performance status of 0-3
- Subject must have adequate bone marrow* without growth factor support as follows:
- Absolute Neutrophil Count (ANC) ≥ 1000/μL
Show all 22Show fewer
- Platelets ≥ 75,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening)
- Hemoglobin ≥ 9.0 g/dL * These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias.
- Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
- Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
- Calculated creatinine clearance ≥ 40 mL/min; determined via the Cockcroft-Gault formula.
- AST and ALT ≤ 3.0 × ULN; Bilirubin ≤ 1.5 × ULN*. Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN
- These criteria may be waived by study investigators if abnormal values believed to be due to lymphoma.
- Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test performed as follows:
- At Screening on a serum sample obtained within 14 days prior to the first study drug administration, and
- Prior to dosing on a urine sample obtained on Cycle 1 Day 1 if it has been > 7 days since obtaining the serum pregnancy test results.
- All female subjects not surgically sterile or postmenopausal (for at least 1 year) and non-vasectomized male subjects must practice at least 1 of the following methods of birth control:
- Total abstinence from sexual intercourse (minimum 1 complete menstrual cycle);
- A vasectomized partner(s);
- Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration;
- Double-barrier method (condoms and diaphragm with spermicidal [sponge, jellies or creams]).
- Ability to understand and willingness to sign IRB-approved informed consent
Who cannot join
- Subject has blastoid-variant mantle cell lymphoma
- Subject requires immediate cytoreduction as determined by study investigators
- Subject has documented CNS involvement of mantle cell lymphoma
- Subject has Ann Arbor stage I or contiguous stage II mantle cell lymphoma
- Subject has an uncontrolled infection
- Subject has HIV infection
Show all 10Show fewer
- All subjects will be screened for Hepatitis B (HBsAg, anti-HBs, anti-HBc IgM and total) and Hepatitis C (antibody or RNA). Subjects who are positive for Hepatitis B by HBsAg or DNA as well as subjects positive for Hepatitis C will be excluded. Subjects with anti-HBc positivity and DNA negative may be included but will be required to undergo monthly HBV DNA testing and liver function liver function testing (AST, ALT, alkaline phosphatase, total bilirubin). Patients with HCV antibody positivity and HCV pcr negativity are eligible to be included.
- Subject requires the use of warfarin
- Subject has received immunization with live virus vaccine within 28 days prior to the first dose of study drug
- A female subject is pregnant or breast-feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
The proposed study is an open-label, single arm phase II study of venetoclax in combination with rituximab in patients over the age of 60 with previously untreated mantle cell lymphoma. The primary objective of the trial is to determine whether the combination of venetoclax with rituximab in this patient population yields a clinically acceptable proportion of overall responses (ORR, assessed by PET/CT with Lugano criteria) without chemotherapy.
Read the detailed description
For young, fit patients with mantle cell lymphoma, intensive chemotherapy and rituximab followed by ASCT is often used to achieve prolonged disease free survival. However, this therapy is not curative and has not been shown to improve overall survival. For older or frail patients, who are ineligible for stem cell transplantation, improved disease free survival can be achieved with chemotherapy and rituximab without ASCT, but at the cost of significant short and long-term toxicity. Venetoclax monotherapy has shown impressive single-agent activity in relapsed and refractory mantle cell lymphoma with low rates of adverse events.
The hypothesis is that initial therapy with venetoclax and rituximab will result in rates of CR and PR that are comparable to historical rates with chemoimmunotherapy. Furthermore, this regimen will have fewer side effects than traditional therapy. Investigators also hypothesize that patients achieving a CR will have long durations of response that will continue after stopping venetoclax.
Study investigators will test this hypothesis with an open label, single arm phase II trial with a target accrual of 40 participants. This study will include patients over age 60 who are not candidates for aggressive upfront therapy . Subjects will receive venetoclax and rituximab for up to 12 cycles of 4 weeks each. All patients will stop venetoclax after 12 cycles. Participants who have stable disease or disease progression after 4 cycles will be removed from the trial in order to receive standard of care chemoimmunotherapy. Participants who do not achieve a CR after 8 cycles of venetoclax and rituximab will receive 4 cycles of standard of care bendamustine in addition to continuing rituximab and venetoclax.
This is the first phase II study of venetoclax and rituximab alone as initial therapy for mantle cell lymphoma. In the relapsed and refractory setting, venetoclax has shown high activity in MCL, and as such is a promising option for a non-chemotherapy approach to upfront treatment.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Venetoclax Oral Tablet [Venclexta]
- 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.
Venetoclax Oral Tablet [Venclexta]Drug
Also called rituximab infusion [Rituxan], Bendamustine infusion
Sequential dose levels for Venetoclax dependent on patient response. Fixed doses of 375 mg/m2 rituximab. Fixed dose of Bendamustine 90 mg/m2 added for those with continued PR at Cycle 8
| Study group | Role | What they receive |
|---|---|---|
| venetoclax and rituximab in patients over 60 yrs old with previously untreated mantle cell lymphoma | Experimental | Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2. Receives: Drug: Venetoclax Oral Tablet [Venclexta] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) After Four Cycles of Venetoclax and Rituximab.
The ORR will be the sum of complete (CR) and partial responses (PR)as determined by PET/CT and Lugano criteria. Simon's optimal two-stage design will be used to test the null hypothesis that the true ORR is 50% or less (not considered clinically acceptable).
Measured: 120 days
Secondary outcomes (9)
Complete Response
Complete Response as determined by PET/CT and Lugano criteria after four cycles
Measured: 120 days
Partial Response
Partial Response as determined by PET/CT and Lugano criteria after four cycles
Measured: 120 days
Stable Disease
Stable disease as determined by PET/CT and Lugano criteria after four cycles
Measured: 120 days
Disease Progression
Disease progression as determined by PET/CT and Lugano criteria after four cycles
Measured: 120 days
Complete Response After 8 Cycles of Venetoclax and Rituximab
Complete Response as determined by PET/CT and Lugano criteria after 8 cycles of venetoclax and rituximab
Measured: 240 days
Partial Response After 8 Cycles of Venetoclax and Rituximab
Partial Response as determined by PET/CT and Lugano criteria after 8 cycles of venetoclax and rituximab
Measured: 240 days
Rate of Progression Free Survival (PFS)
To evaluate the progression free survival (PFS) in the intent to treat (ITT) population
Measured: 240 days
Overall Survival (OS)
To evaluate the overall survival (OS) in the intent to treat (ITT) population
Measured: 240 days
Duration of Response (DOR)
To evaluate the duration of response (DOR) for participants achieving a CR or PR
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start21 Jun 2022
- Primary completion14 May 2025
- Study completion14 May 2025
Why it stopped: The study sponsor withdrew funding early, forcing this study to stop all activity and close pre-maturely.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Sequential
- Model description
- Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Lode Swinnen, MD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05025423
- Sponsor's protocol ID
- J2146
- Other IDs
- IRB00288478
- Status last verified
- Jun 2026
- First submitted
- 26 Aug 2021
- Last updated
- 10 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- 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 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT05025423
- Acronym / sponsor ID
- J2146
- Conditions
- Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study sponsor withdrew funding early, forcing this study to stop all activity and close pre-maturely.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 21 Jun 2022 (actual)
- Primary completion
- 14 May 2025 (actual)
- Study completion
- 14 May 2025 (actual)
- First posted
- 27 Aug 2021 (actual)
- Results
- Posted 9 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is an open-label, single arm phase II study of venetoclax in combination with rituximab in patients over the age of 60 with previously untreated mantle cell lymphoma. The primary objective of the trial is to determine whether the combination of venetoclax with rituximab in this patient population yields a clinically acceptable proportion of overall responses (ORR, assessed by PET/CT with Lugano criteria) without chemotherapy.
Detailed description
For young, fit patients with mantle cell lymphoma, intensive chemotherapy and rituximab followed by ASCT is often used to achieve prolonged disease free survival. However, this therapy is not curative and has not been shown to improve overall survival. For older or frail patients, who are ineligible for stem cell transplantation, improved disease free survival can be achieved with chemotherapy and rituximab without ASCT, but at the cost of significant short and long-term toxicity. Venetoclax monotherapy has shown impressive single-agent activity in relapsed and refractory mantle cell lymphoma with low rates of adverse events.
The hypothesis is that initial therapy with venetoclax and rituximab will result in rates of CR and PR that are comparable to historical rates with chemoimmunotherapy. Furthermore, this regimen will have fewer side effects than traditional therapy. Investigators also hypothesize that patients achieving a CR will have long durations of response that will continue after stopping venetoclax.
Study investigators will test this hypothesis with an open label, single arm phase II trial with a target accrual of 40 participants. This study will include patients over age 60 who are not candidates for aggressive upfront therapy . Subjects will receive venetoclax and rituximab for up to 12 cycles of 4 weeks each. All patients will stop venetoclax after 12 cycles. Participants who have stable disease or disease progression after 4 cycles will be removed from the trial in order to receive standard of care chemoimmunotherapy. Participants who do not achieve a CR after 8 cycles of venetoclax and rituximab will receive 4 cycles of standard of care bendamustine in addition to continuing rituximab and venetoclax.
This is the first phase II study of venetoclax and rituximab alone as initial therapy for mantle cell lymphoma. In the relapsed and refractory setting, venetoclax has shown high activity in MCL, and as such is a promising option for a non-chemotherapy approach to upfront treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2.
| Arm | Type | Receives |
|---|---|---|
| venetoclax and rituximab in patients over 60 yrs old with previously untreated mantle cell lymphoma | Experimental | Drug: Venetoclax Oral Tablet [Venclexta]Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma as defined by the World Health Organization (WHO) classification scheme.
- Age ≥ 60
- Subjects must be previously untreated for mantle cell lymphoma and deemed to require treatment by the treating physician
- ECOG performance status of 0-3
- Subject must have adequate bone marrow* without growth factor support as follows:
Key exclusion criteria (10 listed)
- Subject has blastoid-variant mantle cell lymphoma
- Subject requires immediate cytoreduction as determined by study investigators
- Subject has documented CNS involvement of mantle cell lymphoma
- Subject has Ann Arbor stage I or contiguous stage II mantle cell lymphoma
- Subject has an uncontrolled 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 |
|---|---|---|
| Venetoclax Oral Tablet [Venclexta]Also: rituximab infusion [Rituxan], Bendamustine infusionSequential dose levels for Venetoclax dependent on patient response. Fixed doses of 375 mg/m2 rituximab. Fixed dose of Bendamustine 90 mg/m2 added for those with continued PR at Cycle 8 | Drug | venetoclax and rituximab in patients over 60 yrs old with previously untreated mantle cell lymphoma |
Primary outcome
Overall Response Rate (ORR) After Four Cycles of Venetoclax and Rituximab.
Time frame: 120 days
The ORR will be the sum of complete (CR) and partial responses (PR)as determined by PET/CT and Lugano criteria. Simon's optimal two-stage design will be used to test the null hypothesis that the true ORR is 50% or less (not considered clinically acceptable).
9 secondary outcomes
Complete Response
Time frame: 120 days
Partial Response
Time frame: 120 days
Stable Disease
Time frame: 120 days
Disease Progression
Time frame: 120 days
Complete Response After 8 Cycles of Venetoclax and Rituximab
Time frame: 240 days
Partial Response After 8 Cycles of Venetoclax and Rituximab
Time frame: 240 days
Rate of Progression Free Survival (PFS)
Time frame: 240 days
Overall Survival (OS)
Time frame: 240 days
Duration of Response (DOR)
Time frame: 25 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
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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.
Lode Swinnen, MD principal investigator
Johns Hopkins School of Medicine
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 Venetoclax Oral Tablet [Venclexta] in people with Mantle Cell Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 22 inclusion and 10 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: stopped early, as of the sponsor's last update on 10 Jun 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?
Yes. Results are posted in the registry (first posted 9 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) After Four Cycles of Venetoclax and Rituximab. (time frame: 120 days). 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 Jun 2026.