- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03623373
Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma
February 9, 2024 updated by: Washington University School of Medicine
A Pilot Study of Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma
This study is designed to evaluate the efficacy and safety of acalabrutinib plus bendamustine and rituximab followed by acalabrutinib plus cytarabine and rituximab in subjects with treatment naïve mantle cell lymphoma (MCL), as a preparation for a larger cooperative group trial with the goal of achieving a standard induction regimen for MCL in transplant eligible patients.
The investigators hypothesize that the addition of acalabrutinib to BR/CR regimen will prove safe and increase the complete response (CR) rate as well as minimal residual disease (MRD) negativity pre-transplant, thus improving clinical outcomes.
Study Overview
Status
Active, not recruiting
Conditions
Study Type
Interventional
Enrollment (Actual)
13
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Histologically confirmed mantle cell lymphoma with documented expression of Cyclin D1 by immune-histochemical stains and/or t(11;14) by cytogenetics or FISH.
- Presence of evaluable disease by PET imaging per the Lugano classification.
- Eligible for autologous stem cell transplantation.
- Between 18 and 70 years of age, inclusive.
- ECOG performance status ≤ 2
Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,000/mcL unless, in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement
- Platelets ≥ 100,000/mcL unless, in the opinion of the treating physician, thrombocytopenia is due to splenomegaly or bone marrow involvement
- Total bilirubin ≤ 2.0 x IULN and AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN except when, in the opinion of the treating physician, elevation is due to direct involvement of lymphoma (e.g. hepatic infiltration or biliary obstruction due to lymphoma) or Gilbert's disease
- Creatinine ≤ IULN OR creatinine clearance ≥ 40 mL/min for patients with creatinine levels above institutional normal
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Any previous chemotherapy or radiation for mantle cell lymphoma. Short course of steroids for symptom relief prior to presentation is permissible.
- Symptomatic meningeal or parenchymal brain lymphoma.
- Prior exposure to a BTK inhibitor.
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to acalabrutinib, rituximab, cytarabine, bendamustine, or other agents used in the study.
- Received a live virus vaccination within 28 days of first dose of study drug.
- Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec at screening. Exception: subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN. Exception: Subjects receiving warfarin are excluded; however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion with the PI.
- Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
- History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
- Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- Subjects with serologic status reflecting active viral hepatitis B or C infection. Subjects who are hepatitis B core antibody positive but surface antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positive patients will be excluded. Subjects who are hepatitis C antibody positive will need negative PCR prior to enrollment. Subjects with positive hepatitis C PCR will be excluded.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with acalabrutinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bendamustine/Rituximab/Acalabrutinib/Cytarabine
|
Bendamustine will be administered at a dose of 90 mg/m^2 IV over 30 minutes on Days 1 and 2 of Cycles 1-3
Other Names:
In Cycle 1, rituximab will be administered at a dose of 375 mg/m^2 IV on Day 1 or 2 at the investigator's discretion in order to reduce the risk of a first infusion reaction.
Rituximab will be given on Day 1 of Cycles 1 through 6.
Other Names:
The capsules should be swallowed intact with water and with or without food.
Other Names:
On Days 1 and 2 of Cycles 4-6, following rituximab dosing, cytarabine will be administered IV every 12 hours for a total of 4 doses.
Other Names:
Until collection of ≥ 2 x 106 CD34+ stem cells / kg
-Baseline, end of Cycle 3, 4-6 weeks after Cycle 6 Day 1, and if the patient discontinues protocol therapy prior to completion of Cycle 6
-Baseline
-Bone marrow will be collected at baseline if the patient requires a marrow for staging purposes and at end of treatment if the patient requires a marrow for restaging.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stem Cell Mobilization Success Rate With Cytarabine and Rituximab
Time Frame: Through 5 courses of apheresis (up to 5 days)
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-Stem cell mobilization success is defined as a yield of >2x10^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis
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Through 5 courses of apheresis (up to 5 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of Regimen in Subjects With MCL as Measured by Treatment Related Non-hematologic Toxicity of Grade 3 or Higher
Time Frame: 30 days following completion of treatment (estimated to be 7 months)
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-Toxicity is measured using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
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30 days following completion of treatment (estimated to be 7 months)
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Overall Response Rate (ORR = Complete Response (CR) + Partial Response (PR)) of Subjects
Time Frame: Through completion of treatment (estimated to be 6 months)
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-For definitions of CR and PR please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
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Through completion of treatment (estimated to be 6 months)
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Pre-transplant Complete Response Rate
Time Frame: Through completion of treatment (estimated to be 6 months)
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-For definitions of CR, please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
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Through completion of treatment (estimated to be 6 months)
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Progression-free Survival (PFS)
Time Frame: Through 5 years
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Through 5 years
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Overall Survival (OS)
Time Frame: Through 5 years
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-OS=time from study registration until death from any cause
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Through 5 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Brad S Kahl, M.D., Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 29, 2018
Primary Completion (Actual)
February 9, 2020
Study Completion (Estimated)
February 5, 2025
Study Registration Dates
First Submitted
July 26, 2018
First Submitted That Met QC Criteria
August 7, 2018
First Posted (Actual)
August 9, 2018
Study Record Updates
Last Update Posted (Estimated)
February 13, 2024
Last Update Submitted That Met QC Criteria
February 9, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Mantle-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Immunological
- Bendamustine Hydrochloride
- Rituximab
- Cytarabine
- Acalabrutinib
Other Study ID Numbers
- 201809111
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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