Clinical Trials /

Acalabrutinib-Lenalidomide-Rituximab in Patients With Untreated MCL

NCT03863184

Description:

This is a single-arm phase 2 study to evaluate the preliminary evidence of efficacy and safety of the combination of acalabrutinib, lenalidomide and rituximab (ALR) in previously untreated mantle cell lymphoma. The study includes an induction phase consisting of 12 cycles of ALR. Responding subjects will be eligible to enter a maintenance phase. Subjects will continue maintenance ALR until disease progression, development of unacceptable toxicity, or voluntary withdrawal. Subjects will be followed after completing study intervention every 6 months for alternate anti-cancer therapy and survival.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Acalabrutinib-Lenalidomide-Rituximab in Patients With Untreated MCL
  • Official Title: A Multiple-center Phase 2 Study of Acalabrutinib-Lenalidomide-Rituximab in Patients With Previous Untreated Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 1807019439
  • NCT ID: NCT03863184

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
AcalabrutinibCALQUENCE, ACP-196ALR in Combination
LenalidomideRevlimidALR in Combination
RituximabRituxanALR in Combination

Purpose

This is a single-arm phase 2 study to evaluate the preliminary evidence of efficacy and safety of the combination of acalabrutinib, lenalidomide and rituximab (ALR) in previously untreated mantle cell lymphoma. The study includes an induction phase consisting of 12 cycles of ALR. Responding subjects will be eligible to enter a maintenance phase. Subjects will continue maintenance ALR until disease progression, development of unacceptable toxicity, or voluntary withdrawal. Subjects will be followed after completing study intervention every 6 months for alternate anti-cancer therapy and survival.

Detailed Description

      This is a single-arm phase 2 study to evaluate the preliminary evidence of efficacy and
      safety of the combination of acalabrutinib, lenalidomide and rituximab (ALR) in previously
      untreated mantle cell lymphoma.

      The study includes an induction phase consisting of 12 cycles of ALR. Responding subjects
      will be eligible to enter a maintenance phase. Subjects will continue maintenance ALR until
      disease progression, development of unacceptable toxicity, or voluntary withdrawal. Subjects
      in complete response wishing to attempt stem cell collection following at least 6 months of
      induction treatment can hold lenalidomide for up to 30 days, and restart following stem cell
      collection.

      Subjects will be monitored for Minimal Residual Disease (MRD) status in peripheral blood at
      baseline and completion of 12 cycles of induction treatment using Adaptive Biotechnology
      Clonoseq assay, and then every 4 cycles.

      Subjects will be followed after completing study intervention every 6 months for alternate
      anti-cancer therapy and survival.
    

Trial Arms

NameTypeDescriptionInterventions
ALR in CombinationExperimentalAcalabrutinib, lenalidomide, and rituximab in combination
  • Acalabrutinib
  • Lenalidomide
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of mantle cell lymphoma

          -  Age ≥ 18 years

          -  No prior systemic therapy for lymphoma

          -  Measurable disease defined by a tumor mass ≥ 1.5 cm in one dimension and measurable in
             two dimensions; measurable spleen disease is allowed

          -  Treatment should be indicated according to the treating physician

          -  ECOG performance status ≤ 2

          -  Required initial laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥ 1000 cells/mm3

               -  Platelet count ≥ 75,000 cells/mm3

               -  Calculated creatinine clearance ≥ 30 ml/min by Cockcroft-Gault formula

               -  Total bilirubin ≤ 2.0 x ULN

               -  AST/SGOT and ALT/SGPT ≤ 3.0 x ULN

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
             intolerant to ASA may use low molecular weight heparin).

          -  All subjects must be registered into the mandatory Revlimid REMS® program, and be
             willing and able to comply with the requirements of Revlimid REMS®.

          -  Patients of reproductive potential agree to use birth control throughout their
             participation in this study, and for 28 days following study termination.

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program. Females of childbearing potential (FCBP) must
             have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL
             within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for
             Cycle 1 (prescriptions must be filled within 7 days). FCBP must either commit to
             continued abstinence from heterosexual intercourse or begin TWO acceptable methods of
             birth control, one highly effective method and one additional effective method AT THE
             SAME TIME, at least 28 days before and continue for at least 28 days after the last
             dose of lenalidomide (or 2 days after the last dose of acalabrutinib, whichever is
             longer). FCBP must also agree to ongoing pregnancy testing. Men must agree to use a
             latex condom during sexual activity with a FCBP through one week post last dose even
             if they have had a successful vasectomy. Men must also agree to refrain from sperm
             donation during the same timeframe. See Appendix: Risks of Fetal Exposure, Pregnancy
             Testing Guidelines and Acceptable Birth Control Methods.

          -  Understand and voluntarily sign an ICF prior to any study related assessments and
             procedures are conducted.

          -  Able to adhere to the study visit schedule and other protocol requirements.

        Exclusion Criteria:

          -  Patients with blastoid histology

          -  Patients with known or suspected CNS involvement

          -  Viral infection with HIV or hepatitis type B or C. Seropositive HBV patients are
             eligible if they are negative for HBV DNA by PCR and receive concomitant antiviral
             therapy during treatment and for additional six months after coming off study.

          -  Prior history of malignancies other than MCL unless the patient has been disease free
             for ≥ 5 years from the signing of the ICF. Exceptions include basal cell carcinoma or
             squamous cell carcinoma of the skin; carcinoma in situ of cervix; carcinoma in situ of
             breast, or localized prostate cancer

          -  Active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing
             signs/symptoms related to the infection without improvement despite appropriate
             antibiotics, antiviral therapy and/or other treatment)

          -  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.

          -  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 (e.g., hemophilia or von Willebrand
             disease).

          -  Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic
             purpura).

          -  Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
             Patients on moderate CYP3A inhibitors can be considered for study after a washout
             period of at least 7 days.

          -  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.

          -  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.

          -  Patients with a history of toxic epidermal necrolysis or Stevens-Johnson syndrome

          -  Patients that are pregnant or breast feeding

          -  Known hypersensitivity to any study drug or excipients

          -  Patient on corticosteroids within two weeks prior to study entry, except for
             prednisone ≤ 20 mg/day or equivalent for purposes other than treating MCL

          -  Use of any other experimental drug or therapy within 28 days of baseline

          -  Patient at high risk for deep vein thrombosis not willing to take DVT prophylaxis

          -  Any significant medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from participating in the study

          -  Known prior exposure to BTK inhibitor
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Peripheral blood minimum residual disease (MRD)-negative complete response (CR) rate of the combination of acalabrutinib + lenalidomide + rituximab at the conclusion of 12 cycles of induction therapy
Time Frame:1 year
Safety Issue:
Description:Percentage of subjects with MRD-negative CR at the conclusion of 12 cycles of induction therapy. Each cycle is 28 days, 12 cycles is approximately 1 year.

Secondary Outcome Measures

Measure:Safety of combination treatment with acalabrutinib, lenalidomide, and rituximab as measured by the percentage of subjects that experience 1 or more adverse event
Time Frame:4 years
Safety Issue:
Description:Rate of subjects that experience 1 or more adverse events
Measure:Overall response rate
Time Frame:4 years
Safety Issue:
Description:Rate of subjects who achieve a partial or complete response
Measure:Complete response rate
Time Frame:4 years
Safety Issue:
Description:Rate of subjects who achieve a complete response
Measure:Progression free survival
Time Frame:4 years
Safety Issue:
Description:Measured from start of treatment to time of progression or death from any cause, measured in months
Measure:Overall survival
Time Frame:4 years
Safety Issue:
Description:Measured from start of treatment to death from any cause, measured in months

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • MRD
  • Minimal-residual-disease
  • Treatment naive
  • Untreated
  • Frontline
  • Acalabrutinib
  • Lenalidomide
  • Rituximab

Last Updated

October 11, 2019