Acalabrutinib-Lenalidomide-Rituximab in Patients With Untreated MCL

NCT03863184 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 1807019439
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-arm phase 2 study to evaluate the preliminary evidence of efficacy and safety of the combination of acalabrutinib, lenalidomide and rituximab (ALR) and acalabrutinib, lenalidomide and obinutuzumab (ALO) in previously untreated mantle cell lymphoma. The study includes an induction phase consisting of 12 cycles of ALR or ALO. Responding subjects will be eligible to enter a maintenance phase. Subjects will continue maintenance ALR or ALO 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.

Conditions

Mantle Cell Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (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

  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.

  1 year

Secondary Outcomes (6)

• Safety of Combination Treatment With Acalabrutinib, Lenalidomide, and Rituximab as Measured by the Percentage of Subjects That Experience 1 or More Adverse Event

  4 years

• Overall Response Rate

  4 years

• Complete Response Rate

  4 years

• Progression Free Survival

  4 years

• Overall Survival

  4 years

Study Arms (2)

ALR in Combination

EXPERIMENTAL

Acalabrutinib, lenalidomide, and rituximab in combination

Drug: Acalabrutinib; Drug: Lenalidomide; Drug: Rituximab

ALO in Combination

EXPERIMENTAL

Acalabrutinib, lenalidomide and obinutuzumab in combination

Drug: Acalabrutinib; Drug: Lenalidomide; Drug: Obinutuzumab

Interventions

Acalabrutinib DRUG

Acalabrutinib, oral, 100 mg BID, continuous

Also known as: CALQUENCE, ACP-196

ALO in Combination; ALR in Combination

Lenalidomide DRUG

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

Also known as: Revlimid

ALO in Combination; ALR in Combination

Rituximab DRUG

Rituximab, IV, weekly during Cycle 1, and every other cycle starting with Cycle 4

Also known as: Rituxan

ALR in Combination

Obinutuzumab DRUG

Obinutuzumab on days 1, 8, 15 of cycle 1, day 1 of cycles 2-6, then every 2 cycles

Also known as: Gazyva

ALO in Combination

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• AstraZeneca: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (1)

• Ruan J, Bond DA, Shah B, Allan JN, Rutherford SC, Gribbin C, Chen Z, Bhinder B, Tam W, Rossi D, Xiang J, Hobbie B, Harbhajan M, Sahni TK, Chen GZ, Sigouros M, Inghirami G, Chen-Kiang S, Elemento O, Maddocks K, Leonard JP, Martin P. MRD-driven initial therapy of acalabrutinib and lenalidomide plus rituximab or obinutuzumab for mantle cell lymphoma. Blood Adv. 2026 Feb 24;10(4):1381-1394. doi: 10.1182/bloodadvances.2025017760.

  PMID: 41289154 DERIVED

Related Links

• WCM Joint Clinical Trials Office

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Neoplasm, Residual

Interventions

acalabrutinib; Lenalidomide; Rituximab; obinutuzumab

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jia Ruan, MD, PhD
• Organization: Weill Cornell Medicine

jruan@med.cornell.edu

646-962-2064

Study Officials

• Jia Ruan, M.D., Ph.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 5, 2019
• Study Start: October 11, 2019
• Primary Completion: April 25, 2024
• Study Completion (Estimated): May 30, 2028
• Last Updated: April 28, 2026
• Results First Posted: June 6, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)