Chronic Lymphocytic LeukemiaPhase 2NCT03609593
Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic Leukemia
A Phase 2 study testing Bendamustine, Venetoclax and Rituximab in people with Chronic Lymphocytic Leukemia, run by Nicole Lamanna at 1 site in United States.
Trial summary
The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Bendamustine, Venetoclax and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2018to 27 Jan 2026
- Phase
- Phase 2
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years of age.
- Diagnosed with CLL
- To be considered CLL, the subject must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells.
- Histologic and immunophenotypic analysis should demonstrate small to moderate size lymphocytes with flow cytometry demonstrating a certain population of lymphocytes.
- No prior therapy for their disease. Topical or inhaled corticosteroids are permitted for other medical conditions, ie asthma or dermatologic reasons.
- Eastern Oncology Cooperative Group (ECOG) performance score of ≤ 2.
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- Subjects with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment on this protocol regardless of disease stage upon discussion with the principal investigator.
- An absolute neutrophil count > 1.0 109/L; hemoglobin > 8 g/dL; or a platelet count > 50 x 109/L (unless due to bone marrow failure).
- Adequate hepatic function
- activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5x the upper limit of reference ranges.
- Ability to understand and the willingness to sign a written informed consent document.
- Women of child-bearing potential and men must agree to use adequate contraception (see below) for at least 90 days prior to study entry and for the duration of study participation.
- For women of childbearing potential (WCBP): a negative serum β-human chorionic gonadotropin (βhCG) pregnancy test must be performed within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women ≤ 55 years] or 12 consecutive months [women > 55 years]).
- Male and female subjects who are not surgically sterile or postmenopausal must be willing to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of study drug. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception.
Who cannot join
- Subjects who have been previously treated for CLL or small lymphocytic lymphoma (SLL), except with corticosteroids for symptom relief.
- Treatment with any of the following within 7 days prior to the first dose of study drug:
- Steroid therapy for anti-neoplastic intent
- moderate or strong cytochrome P450 3A (CYP3A) inhibitors
- moderate or strong CYP3A inducers
- Subject has known allergy to both xanthine oxidase inhibitors and/or rasburicase.
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- Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.
- Subject has evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
- Subject is known to be positive for HIV. (HIV testing is not required.)
- New York Heart Association (NYHA) class II-IV heart failure or arrhythmia requiring treatment.
- Pregnant or lactating women. Women and men of childbearing age should use effective contraception.
- Subject has a history of active malignancies other than CLL within the past 2 years prior to study entry with the exception of: adequately treated in situ carcinoma of the cervix uteri, adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Subjects may receive intravenous immunoglobulin (IVIG) for hypogammaglobulinemia while on protocol. Subjects may receive erythropoietin, filgrastim, pegfilgrastim, or sargramostim while on protocol.
- Subject has malabsorption syndrome or other condition that precludes enteral route of administration.
- Subjects with known Richter's syndrome or a history of Richter's syndrome.
- Subjects who are are actively being treated for a non-hematologic autoimmune disease, or are on other immunomodulatory agents (e.g. cyclosporine, tacrolimus, etc.) will be excluded.
- Subjects who have received an allogeneic stem cell transplant.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to BCL-2 inhibitors, bendamustine, or anti-CD20 monoclonal antibodies.
- Administration or consumption of any of the following within 3 days prior to the first dose of study drug:
- Grapefruit or grapefruit products
- Seville oranges (including marmalade containing Seville oranges)
- Star fruit
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center / NewYork-Presbyterian Hospital
New York, New York, 10032
About this study
Official title: A Single-arm, Multi-center Phase II Trial of Bendamustine/Rituximab Induction Followed by Venetoclax and Rituximab Consolidation for the Frontline Treatment of Chronic Lymphocytic Leukemia (CLL)
The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 [del(17p)]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.
Read the detailed description
This is a single arm multicenter phase II study using bendamustine-rituximab (BR) followed by venetoclax and rituximab for the upfront treatment of chronic lymphocytic leukemia (CLL). The activity, safety, and survival data have been presented previously for BR alone in patients with previously untreated disease and venetoclax alone in relapsed/refractory patients and those with high-risk disease. After pretreatment evaluation, patients will receive three cycles of BR followed by venetoclax via a five-week dose escalation to 400 mg daily. Once patients reach 400 mg of venetoclax daily, patients will receive six cycles (months) of rituximab as consolidation. Total time of venetoclax therapy will be 12 cycles and total time on therapy (BR plus venetoclax plus rituximab) will be 15 cycles. Responses and endpoints will be assessed after 3, 6, 9 (laboratory only), 12, 18, 24, 30, and 36 cycles. Minimal residual disease (MRD) testing will be done after 3, 6, 9, 12, 18, and 24 cycles via an 8-color flow cytometry panel. Bone marrow testing for MRD can be performed if the peripheral blood is MRD negative (or was MRD negative at the last test). Anti-infective prophylaxis against H. zoster and P. jiroveci will be mandated. Tumor lysis syndrome (TLS) prophylaxis with allopurinol and/or an alternative will be mandated.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Bendamustine, Venetoclax, Rituximab
- Keywords
- Chronic Lymphocytic Leukemia (CLL), Leukemia, Bendamustine, Rituximab, Venetoclax
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Treanda
Subjects will receive Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days.
VenetoclaxDrug
Also called ABT-199, Venclexta
Venetoclax: 12 cycles
Venetoclax will then be started after 3 cycles of BR. Dosing for venetoclax will be in a step wise fashion as follows:
- Cycle 4 days 1-7 (Week 1): 20 mg once daily
- Cycle 4 days 8-14 (Week 2): 50 mg once daily
- Cycle 4 days 15-21 (Week 3): 100 mg once daily
- Cycle 4 days 22-28 (Week 4): 200 mg once daily
- Cycle 4 day 29 and thereafter (Week 5 and on): 400 mg once daily; continue until disease progression, unacceptable toxicity, or 12 cycles duration.
RituximabDrug
Also called Rituxan
For cycles 1 through 3, subjects will receive BR on days 1 and 2. For cycles 5-10, subjects will receive rituximab monotherapy at 375 mg/m2 (cycle 5) or rituximab at 500 mg/m2 (cycles 6-10) on day 1 (or days 1 and 2 if split-dose).
| Study group | Role | What they receive |
|---|---|---|
| BR followed by venetoclax and rituximab | Experimental | Subjects will be on Bendamustine 50-90 mg/m2 on days 1-2 for three cycles with each cycle being 28 days, and Rituximab 375 mg/m2 on day 1 or days 1-2 for three cycles with each cycle being 28 days. Venetoclax will then be started in a step-wise fashion per the package insert. Receives: Drug: Bendamustine; Drug: Venetoclax; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) After the Completion of All Therapy
Number of patients with reduction in tumor burden of a predefined amount
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2018
- Study start12 Nov 2018
- Primary completion27 Jan 2026
- Study completion27 Jan 2026
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 Chronic Lymphocytic LeukemiaStudies 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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nicole Lamanna
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicole Lamanna, Columbia University
- Investigators
- Nicole Lamanna, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03609593
- Sponsor's protocol ID
- AAAR6357
- Status last verified
- Sep 2026
- First submitted
- 25 Jul 2018
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No