Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic Leukemia

  • STATUS
    Recruiting
  • End date
    Dec 14, 2025
  • participants needed
    25
  • sponsor
    Nicole Lamanna
Updated on 14 October 2021
platelet count
cancer
corticosteroids
lymphoid leukemia
anemia
chronic lymphocytic leukemia
rituximab
flow cytometry
thrombocytopenia
venetoclax
neutrophil count
bendamustine
lymphocytosis

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. 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.

Description

This is a single-center 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 months and total time on therapy (BR plus venetoclax plus rituximab) will be 15 months. 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.

Details
Condition Chronic Lymphocytic Leukemia, Lymphocytic Leukemia, Chronic, leukemia chronic lymphocytic, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma
Treatment Rituximab, Bendamustine, venetoclax
Clinical Study IdentifierNCT03609593
SponsorNicole Lamanna
Last Modified on14 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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 -human chorionic gonadotropin (hCG) 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

Exclusion Criteria

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
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
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