CCND1 PositivePhase 2NCT03872180
Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
A Phase 2 study testing Bendamustine, Obinutuzumab and Venetoclax in people with CCND1 Positive and Mantle Cell Lymphoma, run by Emory University at 3 sites in United States.
Trial summary
This phase II trial studies how well bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CCND1 Positive, Mantle Cell Lymphoma, t(11;14) Positive
- What is being tested?
- Bendamustine, Obinutuzumab and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 Apr 2019to 15 Jul 2027
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form
- Ability and willingness to comply with the requirements of the study protocol
- Histologic diagnosis of mantle cell lymphoma. This diagnosis must be confirmed at the treating center and patients must have this diagnosis confirmed by at least one of the following criteria:
- Fluorescent in situ hybridization (FISH) or conventional cytogenetics positive for t(11;14)
- Cyclin D1 positive by immunohistochemistry
- Documentation by a hematopathologist at the treating institution that there is pathologic evidence of mantle cell lymphoma if neither criteria above are met
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- No previous therapy for diagnosis of lymphoma (note that in patients deemed to be high-risk for tumor lysis syndrome or for rapid clinical deterioration due to symptomatic disease by the investigator, a short course of steroids designed to decrease tumor burden is permitted)
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1.5 x 10⁹/L
- Platelet count ≥ 75 x 10⁹/L
- Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Total bilirubin < 1.5 x ULN (or ≤ 3 x ULN for patients with documented Gilbert syndrome)
- NOTE: Patients with renal or hepatic impairment that is disease-related (ie, hydronephrosis, hepatic involvement) in the opinion of the investigator but who meet all other eligibility criteria may be considered for enrollment in consultation with the investigational new drug (IND) sponsor, Dr. Jonathon Cohen. Documentation of prior adequate renal/hepatic function and clear association with the disease will be required
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer
- A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
- Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of obinutuzumab. Men must refrain from donating sperm during this same period
- With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of obinutuzumab to avoid exposing the embryo
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
Who cannot join
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
- Individuals in documented remission without treatment for ≥ 2 years prior to enrollment may be included at the discretion of the investigator. Patients with more recently treated low risk prostate cancer, thyroid cancer, or ductal carcinoma in situ (DCIS) who are felt to be at low risk for progression and who are not currently taking any chemotherapy, hormonal therapy or other anti-cancer therapy are eligible. Patients who have been treated and been in remission for < 2 years must be cleared with the study chair prior to initiating study therapy
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
- Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
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- Received strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of initiating venetoclax. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to first dose of venetoclax
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody
- Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation
- Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. These patients must be willing to undergo monthly DNA testing and to remain on hepatitis B prophylaxis during therapy
- Patients with human immunodeficiency virus (HIV) are eligible if they have a cluster of differentiation 4 (CD4) count > 400 and an undetectable viral load. They must be under the care of an infectious disease physician and have no history of an acquired immune deficiency syndrome (AIDS)-defining illness (except lymphoma)
- Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
- Pregnant or lactating, or intending to become pregnant during the study
- Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study drug
- Recent major surgery (within 6 weeks prior to the start of cycle 1, day 1) other than for diagnosis or line placement
- Malabsorption syndrome or other condition that precludes enteral route of administration
- Known allergy to both xanthine oxidase inhibitors (ie, allopurinol) and rasburicase
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Emory Johns Creek Hospital
Johns Creek, Georgia, 30097
About this study
Official title: A Phase II Evaluation of Bendamustine, Obinutuzumab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
This phase II trial studies how well bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bendamustine, obinutuzumab, and venetoclax may work better in treating patients with mantle cell lymphoma.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the efficacy of the combination of bendamustine, obinutuzumab and venetoclax in patients with untreated mantle cell lymphoma.
SECONDARY OBJECTIVES:
- To evaluate the safety and dose intensity of the combination of bendamustine, obinutuzumab and venetoclax in untreated mantle cell lymphoma.
II. To explore methods of determining molecular remission for patients with untreated mantle cell lymphoma (MCL).
III. To evaluate long-term outcomes including progression-free and overall survival for patients with untreated MCL who receive the combination.
OUTLINE:
Patients receive venetoclax orally (PO) on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine intravenously (IV) on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up at 45-60 days.
- Conditions
- CCND1 Positive, Mantle Cell Lymphoma, t(11;14) Positive
- Being tested
- Bendamustine, Obinutuzumab, 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.
BendamustineDrug
Also called SDX-105
Given IV
ObinutuzumabBiological
Also called GA-101, Gazyva, RO5072759
Given IV
VenetoclaxDrug
Also called ABT-199, GDC-0199, RG7601, Venclexta
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax, bendamustine, obinutuzumab | Experimental | Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Receives: Drug: Bendamustine; Biological: Obinutuzumab; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Response at Completion of Induction Therapy With This Combination
Response will be assessed by positron emission tomography (PET)/computerized tomography (CT) imaging according to the Lugano Classification for response assessment in lymphoma, developed at the 2014 International Conference on Malignant Lymphoma.
Measured: Up to 2.5 years from study start
Secondary outcomes (5)
Rate of Minimal Residual Disease (MRD) Negative Complete Response by ClonoSEQ Mantle Cell Lymphoma (MCL) Assay
MRD will be assessed by peripheral blood using the ClonoSEQ assay available from Adaptive Biotechnologies.
Measured: Up to 6 years from study start
Overall Response Rate
Will be summarized descriptively.
Measured: Up to 6 years from study start
Time to Tumor Progression
Will be summarized descriptively.
Measured: Up to 6 years from study start
Progression Free Survival (PFS)
Will be described using the Kaplan-Meier methodology. Some patients may undergo consolidative autologous stem cell transplant without evidence of disease progression. This will not be counted against PFS.
Measured: Up to 6 years from study start
Overall Survival
Will be described using the Kaplan-Meier methodology.
Measured: Up to 6 years from study start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2019
- Study start11 Apr 2019
- Primary completion6 Jun 2022
- Study completion15 Jul 2027 (estimated)
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 CCND1 PositiveStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., National Cancer Institute (NCI), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Jonathon Cohen, Emory University
- Investigators
- Jonathon B. Cohen, MD, MS, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03872180
- Sponsor's protocol ID
- IRB00102827
- Other IDs
- NCI-2018-00995, Winship4363-18, ML40204, P30CA138292
- Status last verified
- May 2026
- First submitted
- 11 Mar 2019
- Last updated
- 2 Oct 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 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Evaluation of Bendamustine, Obinutuzumab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT03872180
- Acronym / sponsor ID
- IRB00102827
- Conditions
- CCND1 Positive, Mantle Cell Lymphoma, t(11;14) Positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., National Cancer Institute (NCI), National Institutes of Health (NIH)
- Study start
- 11 Apr 2019 (actual)
- Primary completion
- 6 Jun 2022 (actual)
- Study completion
- 15 Jul 2027 (estimated)
- First posted
- 13 Mar 2019 (actual)
- Results
- Posted 6 Aug 2025
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 bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bendamustine, obinutuzumab, and venetoclax may work better in treating patients with mantle cell lymphoma.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate the efficacy of the combination of bendamustine, obinutuzumab and venetoclax in patients with untreated mantle cell lymphoma.
SECONDARY OBJECTIVES:
- To evaluate the safety and dose intensity of the combination of bendamustine, obinutuzumab and venetoclax in untreated mantle cell lymphoma.
II. To explore methods of determining molecular remission for patients with untreated mantle cell lymphoma (MCL).
III. To evaluate long-term outcomes including progression-free and overall survival for patients with untreated MCL who receive the combination.
OUTLINE:
Patients receive venetoclax orally (PO) on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine intravenously (IV) on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up at 45-60 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax, bendamustine, obinutuzumab | Experimental | Drug: Bendamustine, Biological: Obinutuzumab, Drug: VenetoclaxPatients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Signed informed consent form
- Ability and willingness to comply with the requirements of the study protocol
- Histologic diagnosis of mantle cell lymphoma. This diagnosis must be confirmed at the treating center and patients must have this diagnosis confirmed by at least one of the following criteria:
- No previous therapy for diagnosis of lymphoma (note that in patients deemed to be high-risk for tumor lysis syndrome or for rapid clinical deterioration due to symptomatic disease by the investigator, a short course of steroids designed to decrease tumor burden is permitted)
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2
Key exclusion criteria (18 listed)
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
- Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
- Received strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of initiating venetoclax. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to first dose of venetoclax
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 |
|---|---|---|
| BendamustineAlso: SDX-105Given IV | Drug | Venetoclax, bendamustine, obinutuzumab |
| ObinutuzumabAlso: GA-101, Gazyva, RO5072759Given IV | Biological | Venetoclax, bendamustine, obinutuzumab |
| VenetoclaxAlso: ABT-199, GDC-0199, RG7601, VenclextaGiven PO | Drug | Venetoclax, bendamustine, obinutuzumab |
Primary outcome
Rate of Complete Response at Completion of Induction Therapy With This Combination
Time frame: Up to 2.5 years from study start
Response will be assessed by positron emission tomography (PET)/computerized tomography (CT) imaging according to the Lugano Classification for response assessment in lymphoma, developed at the 2014 International Conference on Malignant Lymphoma.
5 secondary outcomes
Rate of Minimal Residual Disease (MRD) Negative Complete Response by ClonoSEQ Mantle Cell Lymphoma (MCL) Assay
Time frame: Up to 6 years from study start
Overall Response Rate
Time frame: Up to 6 years from study start
Time to Tumor Progression
Time frame: Up to 6 years from study start
Progression Free Survival (PFS)
Time frame: Up to 6 years from study start
Overall Survival
Time frame: Up to 6 years from study start
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for CCND1 Positive
Active, not recruitingPhase 2
Venetoclax and Acalabrutinib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Blastoid Variant Mantle Cell Lymphoma, CCND1 Protein Overexpression
Active, not recruitingPhase 2
Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma
CCND1 Positive, CCND2 Positive
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.
Jonathon B. Cohen, MD, MS principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bendamustine, Obinutuzumab and Venetoclax in people with CCND1 Positive and Mantle Cell Lymphoma, run by Emory University at 3 sites 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 23 inclusion and 18 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 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 6 Aug 2025). 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?
Rate of Complete Response at Completion of Induction Therapy With This Combination (time frame: Up to 2.5 years from study start). 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 2 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.