Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 14 of 32 for:    Acerta Pharma | ( Map: United States )

Acalabrutinib With Alternating Cycles of Bendamustine / Rituximab and Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03623373
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : January 4, 2019
Sponsor:
Collaborator:
Acerta Pharma BV
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE July 26, 2018
First Posted Date  ICMJE August 9, 2018
Last Update Posted Date January 4, 2019
Actual Study Start Date  ICMJE November 29, 2018
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
Stem cell mobilization success rate in subjects with MCL treated with acalabrutinib and an alternating regimen of bendamustine and rituximab with cytarabine and rituximab [ Time Frame: Through 5 courses of apheresis (up to 5 days) ]
-Stem cell mobilization success is defined as a yield of >2x10^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03623373 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
  • Safety and tolerability of acalabrutinib plus BR/CR 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) ]
  • Overall response rate (ORR = complete response (CR) + partial response (PR)) of subjects with MCL treated with acalabrutinib plus BR/CR [ Time Frame: Through completion of treatment (estimated to be 6 months) ]
    -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
  • Pre-transplant complete response rate of subjects with MCL treated with acalabrutinib plus BR/CR [ Time Frame: Through completion of treatment (estimated to be 6 months) ]
    -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
  • Progression-free survival (PFS) of subjects with MCL treated with acalabrutinib plus BR/CR [ Time Frame: Through 5 years ]
    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first
    • London Deauville score of 4 or 5 in individual target nodes/masses with an increase in intensity of uptake from the baseline and/or new FDG avid foci consistent with lymphoma at interim or end of treatment assessment; New FDG avid foci of extranodal disease consistent with lymphoma. If there is concern regarding the etiology of the new lesions, biopsy or interval scan may be considered; New or recurrent FDG avid foci in the bone marrow
  • Overall survival (OS) of subjects with MCL treated with acalabrutinib plus BR/CR [ Time Frame: Through 5 years ]
    -OS=time from study registration until death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Acalabrutinib With Alternating Cycles of Bendamustine / Rituximab and Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma
Official Title  ICMJE A Pilot Study of Acalabrutinib With Alternating Cycles of Bendamustine / Rituximab and Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma
Brief Summary This study is designed to evaluate the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab (BR/CR) 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mantle Cell Lymphoma
Intervention  ICMJE
  • Drug: Bendamustine
    Bendamustine will be administered at a dose of 90 mg/m2 IV over 30 minutes on Days 1 and 2 of Cycles 1, 3, and 5.
    Other Names:
    • Treanda
    • Bendeka
  • Drug: Rituximab
    In Cycle 1, rituximab will be administered at a dose of 375 mg/m2 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 2 through 6.
    Other Names:
    • Rituxan
    • Rituxan Hycela
  • Drug: Acalabrutinib
    The capsules should be swallowed intact with water and with or without food.
    Other Name: Calquence®
  • Drug: Cytarabine
    On Days 1 and 2 of Cycles 2, 4, and 6, following rituximab dosing, cytarabine will be administered IV every 12 hours for a total of 4 doses.
    Other Name: Cytosar-U
  • Procedure: Leukapheresis
    Until collection of ≥ 2 x 106 CD34+ stem cells / kg
  • Procedure: Peripheral blood
    -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
  • Procedure: Oral rinse
    -Baseline
  • Procedure: Bone marrow collection
    -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.
Study Arms  ICMJE Experimental: Bendamustine/Rituximab/Acalabrutinib/Cytarabine
  • Patients will receive (6) 28 day cycles
  • Odd-numbered cycles (1, 3, and 5) will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28.
  • Even-numbered cycles (2, 4, and 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
Interventions:
  • Drug: Bendamustine
  • Drug: Rituximab
  • Drug: Acalabrutinib
  • Drug: Cytarabine
  • Procedure: Leukapheresis
  • Procedure: Peripheral blood
  • Procedure: Oral rinse
  • Procedure: Bone marrow collection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2018)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2025
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 65 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brad S Kahl, M.D. (314) 747-6250 bkahl@wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03623373
Other Study ID Numbers  ICMJE 201809111
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Acerta Pharma BV
Investigators  ICMJE
Principal Investigator: Brad S Kahl, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP