Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Acalabrutinib and Rituximab for the Treatment of Previously 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: NCT04765111
Recruitment Status : Not yet recruiting
First Posted : February 21, 2021
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill cancer cells. Giving acalabrutinib and rituximab may help to control mantle cell lymphoma in elderly patients.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Drug: Acalabrutinib Biological: Rituximab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy measured by complete remission (CR) rate of the acalabrutinib in combination with rituximab in newly diagnosed elderly mantle cell lymphoma (MCL) patients.

II. To determine the safety profile of acalabrutinib with rituximab combination in elderly patients with MCL.

SECONDARY OBJECTIVES:

I. To evaluate the overall response (OR) rate. II. To evaluate the progression-free survival and overall survival. III. To assess serial minimal residual disease (MRD) using clonoseq, circulating tumor deoxyribonucleic acid (ct-DNA) based serial clonal evolution.

IV. Perform baseline genomic profiling for recognizing the predictive signature for response, serial MCL specific analytes assessments while on therapy.

EXPLORATORY OBJECTIVES:

I. Clonal evolution with targeted sequencing (seq) on ctDNA samples in sequential samples using a MCL specific customized gene panel would be assessed.

II. MRD assay using IgH clonoseq and ctDNA analysis, flow cytometry at various time points from peripheral blood (PB)/bone marrow (BM).

III. Sequential immunologic studies with cytokines/chemokines using a analyte panel, T cell numbers, and immunoglobulins (Ig).

IV. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib (A)-rituximab (R) treatment.

V. Extensive bioinformatics studies. VI. Identification of signaling pathways or biomarkers that predict sensitivity after therapy.

OUTLINE:

Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 16, 18, 20, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up at 30 days, every 4 months for 2 years, every 6 months for 2 years, and then annually for 3 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Acalabrutinib Plus Rituximab in Previously Untreated Elderly Patients With Mantle Cell Lymphoma
Estimated Study Start Date : June 30, 2021
Estimated Primary Completion Date : August 22, 2022
Estimated Study Completion Date : August 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Treatment (acalabrutinib, rituximab)
Patients receive acalabrutinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 18, 20, 22, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.
Drug: Acalabrutinib
Given PO
Other Names:
  • ACP-196
  • Bruton Tyrosine Kinase Inhibitor ACP-196
  • Calquence

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab ABBS
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • Rituximab Biosimilar SIBP-02
  • rituximab biosimilar TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima




Primary Outcome Measures :
  1. Complete remission rate [ Time Frame: At 16 weeks ]
  2. Incidence of adverse events (AEs) [ Time Frame: Up to 30 days following the last dose of study drug ]
    Toxicity is defined as all related grade 3 or higher AEs and not only the non-hematologic AEs will be considered toxicities treatment-related grade 3 or higher AEs within the first three cycles, and any treatment-related toxicities, which cause drug delays for more than 4 weeks. Toxicity data by type and severity will be summarized by frequency tables for all patients by Common Terminology Criteria for Adverse Events version 5.0.


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 7 years ]
    Summary statistics including mean, standard deviation, median, and range for continuous variables, frequency count and percentage categorical variables will be reported. Complete response rate and its posterior credibility interval will be calculated. Response rate and its 95% confidence interval will be estimated. Logistic regression model may be fitted to assess the effects of important patient prognostic factors on response.

  2. Progression free survival (PFS) [ Time Frame: From the start of the treatment to progression or death due to any cause whichever happened first, assessed up to 7 years ]
    Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in PFS between patient groups.

  3. Overall survival (OS) [ Time Frame: From the start of the treatment to death due to any cause, assessed up to 7 years ]
    Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in OS between patient groups.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathology confirmed diagnosis of mantle cell lymphoma with CD20 positivity and chromosome translocation t (11;14), (q13;q32) and/or positive cyclin D1 in tissue biopsy
  • Newly diagnosed elderly MCL (age >= 65 years) with no prior therapy under all risk categories
  • Patients with preexisting well-controlled cardio-vascular comorbidities - patients on anticoagulants (excluding warfarin and vitamin K antagonists), antiplatelet, anti-hypertensive, prior ablation, anti-arrhythmia, prior arrhythmias, baseline electrocardiogram (EKG) abnormalities and cardiology clearance are allowed. Ejection fraction >= 50% and cardiology clearance are required
  • Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
  • Bi-dimensional measurable disease using the Cheson criteria (measurable disease by positron emission tomography [PET]-computed tomography [CT] scan defined as at least 1 lesion that measures >= 1.5 cm in single dimension.) Gastrointestinal, bone marrow or spleen only patients are allowable
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 (Patients who have bone marrow and spleen infiltration by MCL are eligible, the ANC and platelets counts will not be limited)
  • Platelet count >= 100,000/mm^3 (Patients who have bone marrow and spleen infiltration by MCL are eligible, the ANC and platelets counts will not be limited)
  • Serum bilirubin =< 1.5 mg/dl
  • Creatinine clearance minimum to 50 mL/min per the Cockcroft-Gault formula
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 x upper limit of normal or =< 5 x upper limit of normal if hepatic metastases are present. Gilbert's disease is allowed
  • Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated with life expectancy of > 3 years. Principal investigator (PI) can use clinical judgement in the best interest of patients
  • Women of childbearing potential (WOBP) must have a negative serum or urine pregnancy test. WOBP and males must be willing to use highly effective methods of birth control. therapy. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib and for 12 months following the last dose of rituximab. For male subjects with a pregnant or non-pregnant WOCBP partner, should use barrier contraception, during treatment and for 2 days after the last dose of acalabrutinib and for 1 month following the last dose of rituximab even if they have had a successful vasectomy

Exclusion Criteria:

  • Patients with central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML) are excluded since those patients have very poor prognosis, need aggressive intensive chemoimmunotherapy and intrathecal chemotherapy along with Bruton's tyrosine kinase (BTK) inhibitors and these patients would not be eligible for this study
  • Pregnant or breast-feeding females
  • Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
  • Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
  • Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x upper limit of normal (ULN)
  • Concurrent participation in another therapeutic clinical trial
  • Immunization with live vaccine within 4 weeks of and during therapy with rituximab
  • Subjects who are hepatitis B or C polymerase chain reaction (PCR) positive. Those with prior hepatitis B (Hep-B) vaccination (i.e., hepatitis B surface antibody [anti-HBs] antibody positive) or natural immunity as evidenced by the presence of anti-HBs and hepatitis B core antibody (anti-HBc) positivity are eligible to enroll. (Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal [GI] consultation)
  • Patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
  • Active bleeding, history of bleeding diathesis (such as Hemophilia or Von-Willbrand disease), any history of intracranial bleed or stroke within 6 months of first dose of study drug
  • Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of acalabrutinib
  • Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug
  • Major surgery within 4 weeks of initiation of therapy
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonist
  • Concomitant use of corticosteroids at > 20 mg prednisone or equivalent per day > 2 weeks
  • Requires treatment with strong CYP3A inhibitors or inducers
  • Patients who have had a stroke within 6 months
  • Any of the following conditions considered clinically significant cardiovascular diseases as determined after cardiology consultation:

    • Diagnosed congestive heart failure
    • Active/symptomatic coronary artery disease
    • Congestive heart failure
    • Myocardial infarction in the preceding 6 months
    • Significant conduction abnormalities, including but not limited to:

      • Left bundle branch block
      • 2nd degree atrioventricular (AV) block type II
      • 3rd degree block
      • QT prolongation (corrected QT [QTc] > 480 msec)
      • Sick sinus syndrome
      • Ventricular tachycardia
      • Symptomatic bradycardia (heart rate < 50 bpm)
      • Persistent, controlled and uncontrolled atrial fibrillation
    • Uncontrolled hypertension
    • Hypotension
    • Light headedness and syncope
  • Active infection
  • Acute infection requiring systemic anti-microbial treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of therapy
  • 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 (2 hours after acalabrutinib/placebo) or antacid (2 hours before or 2 hours after acalabrutinib/placebo). Avoid co-administration with proton pump inhibitors
  • Active infection including systemic fungal or cytomegalovirus (CMV) infection who were hospitalized in past 6 months
  • Any other serious medical condition including, but not limited to, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, uncontrolled hypertension (i.e. uncontrolled blood pressure [BP] - > 160/110 in spite of 3 different classes of full dose anti-hypertensives medications and in spite of cardiology evaluation; documentation from cardiology is required to say that the BP is uncontrollable), chronic obstructive pulmonary disease (COPD), renal failure, psychiatric illness or social circumstances that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form or complying with study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04765111


Contacts
Layout table for location contacts
Contact: Luhua (Michael) Wang 713-792-2860 miwang@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Luhua (Michael) Wang    713-792-2860      
Principal Investigator: Luhua (Michael) Wang         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Luhua (Michael) Wang M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04765111    
Other Study ID Numbers: 2020-0858
NCI-2021-00538 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0858 ( Other Identifier: M D Anderson Cancer Center )
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Acalabrutinib
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents