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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/18/2021.

Acalabrutinib-Lenalidomide-Rituximab in Patients With Untreated MCL

Clinicaltrials.gov identifier NCT03863184

Recruitment Status Recruiting

First Posted March 5, 2019

Last update posted October 15, 2019

Study Description

Brief summary:

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.

  • Condition or Disease:Mantle Cell Lymphoma
  • Intervention/Treatment: Drug: Acalabrutinib
    Drug: Lenalidomide
    Drug: Rituximab
  • Phase: Phase 2
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 24 participants
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: Study intervention begins with an induction phase consisting of 12 cycles of acalabrutinib, lenalidomide, and rituximab (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 CR 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.
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Multiple-center Phase 2 Study of Acalabrutinib-Lenalidomide-Rituximab in Patients With Previous Untreated Mantle Cell Lymphoma
  • Actual Study Start Date: October 2019
  • Estimated Primary Completion Date: November 2022
  • Estimated Study Completion Date: November 2024
Arms and interventions
Arm Intervention/treatment
Experimental: ALR in Combination
Acalabrutinib, lenalidomide, and rituximab in combination
Drug: Acalabrutinib
Acalabrutinib, oral, 100 mg BID, continuous

Drug: Lenalidomide
Lenalidomide, 15 mg for cycle 1, then escalated as tolerated to 20 mg, QD, Days 1-21 out of 28 day cycles

Drug: Rituximab
Rituximab, IV, weekly during Cycle 1, and every other cycle starting with Cycle 4
Outcome Measures
  • Primary Outcome Measures: 1. 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 ]
    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: 1. Complete response rate [ Time Frame: 4 years ]
    Rate of subjects who achieve a complete response
  • 2. Overall survival [ Time Frame: 4 years ]
    Measured from start of treatment to death from any cause, measured in months
  • 3. Progression free survival [ Time Frame: 4 years ]
    Measured from start of treatment to time of progression or death from any cause, measured in months
  • 4. Overall response rate [ Time Frame: 4 years ]
    Rate of subjects who achieve a partial or complete response
  • 5. 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 ]
    Rate of subjects that experience 1 or more adverse events
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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

Contacts and Locations
Contacts

Contact: Amelyn Rodriguez, R.N. 2127461362 amr2017@med.cornell.edu

Contact: Rita Vaccaro, R.N. 2127460702 rig9021@med.cornell.edu

Locations

United States, New York
Weill Cornell Medicine
New York

Sponsors and Collaborators

Weill Medical College of Cornell University

AstraZeneca

Celgene Corporation

Investigators

Principal Investigator: Jia Ruan, M.D., Ph.D. Weill Cornell Medicine

More Information
  • Responsible Party: Weill Medical College of Cornell University
  • ClinicalTrials.gov Identifier: NCT03863184 History of Changes
  • Other Study ID Numbers: 1807019439
  • First Posted: March 5, 2019 Key Record Dates
  • Last Update Posted: October 15, 2019
  • Last Verified: October 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Weill Medical College of Cornell University: MRD
    Minimal-residual-disease
    Treatment naive
    Untreated
    Frontline
    Acalabrutinib
    Lenalidomide
    Rituximab
  • Additional relevant MeSH terms: Lymphoma Lymphoma, Mantle-Cell