Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma

NCT03623373 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201809111
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Stem Cell Mobilization Success Rate With Cytarabine and Rituximab

  -Stem cell mobilization success is defined as a yield of \>2x10\^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis

  Through 5 courses of apheresis (up to 5 days)

Secondary Outcomes (6)

• Safety and Tolerability of Regimen in Subjects With MCL as Measured by Treatment Related Non-hematologic Toxicity of Grade 3 or Higher

  30 days following completion of treatment (estimated to be 7 months)

• Overall Response Rate (ORR = Complete Response (CR) + Partial Response (PR)) of Subjects

  Through completion of treatment (estimated to be 6 months)

• Pre-transplant Complete Response Rate

  Through completion of treatment (estimated to be 6 months)

• Median Progression-free Survival (PFS)

  Up to approximately 5 years of follow-up

• Overall Survival (OS)

  Up to approximately 5 years of follow-up

Study Arms (1)

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

EXPERIMENTAL

* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis

Drug: Bendamustine; Drug: Rituximab; Drug: Acalabrutinib; Drug: Cytarabine; Procedure: Leukapheresis; Procedure: Peripheral blood; Procedure: Oral rinse; Procedure: Bone marrow collection

Interventions

Leukapheresis PROCEDURE

Until collection of ≥ 2 x 106 CD34+ stem cells / kg

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Peripheral blood PROCEDURE

-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

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Oral rinse PROCEDURE

-Baseline

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Bone marrow collection PROCEDURE

-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.

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Bendamustine DRUG

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

Also known as: Treanda, Bendeka

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Rituximab DRUG

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.

Also known as: Rituxan, Rituxan Hycela

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Acalabrutinib DRUG

The capsules should be swallowed intact with water and with or without food.

Also known as: Calquence®

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Cytarabine DRUG

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.

Also known as: Cytosar-U

Bendamustine/Rituximab/Acalabrutinib/Cytarabine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Acerta Pharma BV: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; Rituximab; acalabrutinib; Cytarabine; Leukapheresis; Mouthwashes

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Biomedical and Dental Materials; Specialty Uses of Chemicals; Chemical Actions and Uses; Cosmetics; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Brad S. Kahl, M.D.
• Organization: Washington University School of Medicine

bkahl@wustl.edu

314-273-3591

Study Officials

• Brad S Kahl, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 9, 2018
• Study Start: November 29, 2018
• Primary Completion: February 9, 2020
• Study Completion: April 14, 2025
• Last Updated: April 21, 2026
• Results First Posted: February 2, 2021

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)