LymphomaPhase 2NCT06510309
Rituximab Plus Venetoclax in Front Line Marginal Zone Lymphoma
A Phase 2 study testing Venetoclax and Rituximab in people with Lymphoma and Marginal Zone Lymphoma, run by Gottfried von Keudell, MD PhD at 1 site in United States.
Trial summary
The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating participants with untreated Marginal Zone Lymphoma (MZL). The names of the study drugs involved in this study are: Venetoclax (a type of inhibitor) Rituximab (a type of antibody) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Marginal Zone Lymphoma, MZL
- What is being tested?
- Venetoclax and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2026to 1 Oct 2031
- 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
- Participants must have histologically confirmed Marginal Zone Lymphoma
- Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm or spleen > 13 cm
- Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or colonoscopy with biopsy
- Patients with gastric MALT lymphoma must be h. pylori negative. Patients who are h. pylori positive are allowed if they have failed a trial of h. pylori eradication
- Patients with gastric MALT lymphoma who are h. pylori negative or who relapsed/refractory disease after h. pylori eradication must be ineligible form have refused or failed gastric radiation therapy
- Age ≥18 years
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- ECOG performance status ≤1
- Life expectancy of greater than 2 years
- Participants must meet the following organ and marrow function as defined below:
- Hemoglobin ≥8.0 g/dL
- absolute neutrophil count ≥1,000 cells/mcL (In the event of documented bone marrow involvement, ANC must be ≥1500 cells/mcL)
- platelets ≥50,000 cells/mm3
- total bilirubin < 1.5 x institutional upper limit of normal (ULN) (In patients with Gilberts disease or documented liver involvement, total bilirubin < 3 X ULN will be allowed)
- AST(SGOT)/ALT(SGPT) < 3 × institutional ULN unless elevation is caused by liver involvement with MZL
- Creatinine within institutional ULN OR creatinine clearance >60mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements)
- Ability to understand and the willingness to sign a written informed consent document
- Patient must be able to swallow pills
- HIV-positive patients on combination antiretroviral therapy are eligible if their HIV is under adequate control with an antiretroviral regimen that has been stable for > 4 weeks, as long as the CD4 count is >300. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Patients with Hepatitis B surface antibody serum positivity due to poor immunization, as well as those with Hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible
Who cannot join
- Patients who had prior systemic therapy including rituximab
- Patients who have had prior radiation therapy, with the following exceptions:
- Palliative radiotherapy (RT) is allowed, but must be completed at least 1 week prior to treatment on this study, and prior to any baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT.
- Prior RT for gastric MALT is allowed, but must be completed at least 1 week prior to treatment on this study, and prior to any baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT.
- Prior treatment with ibrutinib or other BTK inhibitor
- Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded unless they are deemed to be unfit for radiation therapy with curative intent.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with uncontrolled hepatitis B or C or HIV infection are ineligible defined as patients with positive serologies and a detectable viral load by PCR.
- Patients with Hep B core ab positivity are allowed provided Hep B PCR is undetectable
- Pregnant women or participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab are excluded from this study because of documented risks of rituximab on fetal immunologic development and unknown effects of venetoclax on embryonic development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued.
- Received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.
- Received moderate or strong CYP3A inducers (such as rifampin, carbamazepine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Gottfried von Keudell, MD, PhD, 617-667-9920, gkeudell@bidmc.harvard.edu
Dea Hunsicker, PhD, dhunsick@bidmc.harvard.edu
About this study
Official title: A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma
The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating participants with untreated Marginal Zone Lymphoma (MZL).
The names of the study drugs involved in this study are:
- Venetoclax (a type of inhibitor)
- Rituximab (a type of antibody)
Read the detailed description
This is a phase II study of rituximab plus venetoclax in participants with MZL who have not had prior chemotherapy. The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating Marginal Zone Lymphoma.
The U.S. Food and Drug Administration (FDA) has not approved venetoclax for MZL but it has been approved for other uses.
The FDA has approved rituximab as a treatment option for MZL.
The research study procedures include screening for eligibility, study treatment visits, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission Tomography (PET) scans, blood tests, bone marrow and tumor biopsies, and electrocardiograms.
Participants will receive study treatment for up to 24 months and will be followed for 1 year after discontinuation of the study drugs.
It is expected that about 33 people will take part in this research study.
Abbvie, Inc. is funding this research study by providing venetoclax.
- Conditions
- Lymphoma, Marginal Zone Lymphoma, MZL
- Being tested
- Venetoclax, Rituximab
- Keywords
- Lymphoma, Marginal Zone Lymphoma, MZL
- Medical subject headings
- Lymphoma, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called ABT-199, GDC-199
B-cell lymphoma inhibitor, tablets taken orally per protocol.
RituximabDrug
Also called Riabni, Ruxience, Truxima, Rituxan
Anti-CD20 monoclonal antibody, 10mL or 50 mL single-use vials, via intravenous (into the vein) infusion per protocol.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab + Venetoclax | Experimental | 33 participants will be enrolled and will complete study procedures as follows:
* Baseline visit with screening assessments, scans, and tumor and bone marrow biopsies.
* Induction Period:
* CT/MRI scans at week 4.
* Weeks 1 - 4: Predetermined dose of Rituximab 1x weekly.
* Weeks 5 - 8: Predetermined dose of Venetoclax 1x daily.
* Maintenance Period:
* CT/MRI scan on weeks 12, 36, 60, 84, and then every 6 months after week 96.
* Predetermined dose of Venetoclax 1x daily for up to week 96, then once every 6 months.
* Predetermined dose of Rituximab 1x weekly at weeks 12, 24, 36, and 48.
* End of Treatment Visit: CT/MRI scan, tumor biopsy, and bone marrow biopsy.
* Follow up: In-clinic visit at 1 year after finishing study drugs. Receives: Drug: Venetoclax; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate (CRR)
Complete Response (CR) rate is defined as the proportion of participants achieving CR during study treatment. CR is defined based on RECIL criteria.
Measured: Up to 24 months
Secondary outcomes (6)
Overall response rate (ORR)
ORR will be measured as the proportion of participants that achieve a PR or CR per RECIL criteria.
Measured: Up to 24 months
Partial Remission (PR) Rate
Partial remission (PR) rate is defined as the proportion of participants achieving partial remission RECIL criteria.
Measured: Up to 24 months
Median Progression Free Survival (PFS)
PFS based on Kaplan-Meier methodology will be measured from the time the participant initiates treatment until the first occurrence of documented progression of disease or death from any cause, censored for participants alive without progression.
Measured: Up to 24 months
Median Overall Survival (OS)
OS based on Kaplan-Meier methodology will be measured from the time the participant initiates treatment until death from any cause, censored for participants alive.
Measured: Up to 36 months
Median Event Free Survival (EFS)
EFS will be measured from the time the participant initiates treatment until documented off therapy for any reason, censored for participants who remain on therapy.
Measured: Up to 24 months
Duration of Response (DOR)
DoR will be measured from the time of initial response until documented progression of disease, censored for participants who remain in response.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2024
- Study start11 Feb 2026
- Primary completionOct 2028 (estimated)
- Study completion1 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- 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
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gottfried von Keudell, MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor-investigator, Gottfried von Keudell, MD PhD, Beth Israel Deaconess Medical Center
- Investigators
- Gottfried von Keudell, MD, PhD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06510309
- Sponsor's protocol ID
- 23-711
- Status last verified
- Mar 2026
- First submitted
- 15 Jul 2024
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
Sharp J, Shana'ah AY, Voorhees TJ, Bond DA, Sawalha Y, Sigmund A, Hanel W, Sehgal L, Alinari L, Baiocchi R, Maddocks K, Jones D, Christian B, Epperla N. Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma. J Natl Compr Canc Netw. 2025 Jun 23;23(7):e257045. doi: 10.6004/jnccn.2025.7045.
PubMed 40550489
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT06510309
- Acronym / sponsor ID
- 23-711
- Conditions
- Lymphoma, Marginal Zone Lymphoma, MZL
- Keywords
- Lymphoma, Marginal Zone Lymphoma, MZL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Gottfried von Keudell, MD PhDUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 11 Feb 2026 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- 1 Oct 2031 (estimated)
- First posted
- 19 Jul 2024 (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.
The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating participants with untreated Marginal Zone Lymphoma (MZL).
The names of the study drugs involved in this study are:
- Venetoclax (a type of inhibitor)
- Rituximab (a type of antibody)
Detailed description
This is a phase II study of rituximab plus venetoclax in participants with MZL who have not had prior chemotherapy. The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating Marginal Zone Lymphoma.
The U.S. Food and Drug Administration (FDA) has not approved venetoclax for MZL but it has been approved for other uses.
The FDA has approved rituximab as a treatment option for MZL.
The research study procedures include screening for eligibility, study treatment visits, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission Tomography (PET) scans, blood tests, bone marrow and tumor biopsies, and electrocardiograms.
Participants will receive study treatment for up to 24 months and will be followed for 1 year after discontinuation of the study drugs.
It is expected that about 33 people will take part in this research study.
Abbvie, Inc. is funding this research study by providing venetoclax.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab + Venetoclax | Experimental | Drug: Venetoclax, Drug: Rituximab33 participants will be enrolled and will complete study procedures as follows: * Baseline visit with screening assessments, scans, and tumor and bone marrow biopsies. * Induction Period: * CT/MRI scans at week 4. * Weeks 1 - 4: Predetermined dose of Rituximab 1x weekly. * Weeks 5 - 8: Predetermined dose of Venetoclax 1x daily. * Maintenance Period: * CT/MRI scan on weeks 12, 36, 60, 84, and then every 6 months after week 96. * Predetermined dose of Venetoclax 1x daily for up to week 96, then once every 6 months. * Predetermined dose of Rituximab 1x weekly at weeks 12, 24, 36, and 48. * End of Treatment Visit: CT/MRI scan, tumor biopsy, and bone marrow biopsy. * Follow up: In-clinic visit at 1 year after finishing study drugs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have histologically confirmed Marginal Zone Lymphoma
- Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm or spleen > 13 cm
- Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or colonoscopy with biopsy
- Patients with gastric MALT lymphoma must be h. pylori negative. Patients who are h. pylori positive are allowed if they have failed a trial of h. pylori eradication
- Patients with gastric MALT lymphoma who are h. pylori negative or who relapsed/refractory disease after h. pylori eradication must be ineligible form have refused or failed gastric radiation therapy
Key exclusion criteria (12 listed)
- Patients who had prior systemic therapy including rituximab
- Patients who have had prior radiation therapy, with the following exceptions:
- Prior treatment with ibrutinib or other BTK inhibitor
- Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded unless they are deemed to be unfit for radiation therapy with curative intent.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| VenetoclaxAlso: ABT-199, GDC-199B-cell lymphoma inhibitor, tablets taken orally per protocol. | Drug | Rituximab + Venetoclax |
| RituximabAlso: Riabni, Ruxience, Truxima, RituxanAnti-CD20 monoclonal antibody, 10mL or 50 mL single-use vials, via intravenous (into the vein) infusion per protocol. | Drug | Rituximab + Venetoclax |
Primary outcome
Complete Response Rate (CRR)
Time frame: Up to 24 months
Complete Response (CR) rate is defined as the proportion of participants achieving CR during study treatment. CR is defined based on RECIL criteria.
6 secondary outcomes
Overall response rate (ORR)
Time frame: Up to 24 months
Partial Remission (PR) Rate
Time frame: Up to 24 months
Median Progression Free Survival (PFS)
Time frame: Up to 24 months
Median Overall Survival (OS)
Time frame: Up to 36 months
Median Event Free Survival (EFS)
Time frame: Up to 24 months
Duration of Response (DOR)
Time frame: Up to 24 months
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 13 Mar 2026.
- Derived from this study: PubMed 40550489Sharp J, Shana'ah AY, Voorhees TJ, Bond DA, Sawalha Y, Sigmund A, Hanel W, Sehgal L, Alinari L, Baiocchi R, Maddocks K, Jones D, Christian B, Epperla N. Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma. J Natl Compr Canc Netw. 2025 Jun 23;23(7):e257045. doi: 10.6004/jnccn.2025.7045.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Gottfried von Keudell, MD, PhD principal investigator
Beth Israel Deaconess Medical 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 Venetoclax and Rituximab in people with Lymphoma and Marginal Zone Lymphoma, run by Gottfried von Keudell, MD PhD 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 19 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 13 Mar 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?
Contact Gottfried von Keudell, MD, PhD (617-667-9920, gkeudell@bidmc.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response Rate (CRR) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06510309, which also lists 1 linked publication.
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 13 Mar 2026.