Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma

NCT04783415 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: 20459NCI-2021-00498P30CA033572
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effects of acalabrutinib, umbralisib, and ublituximab in treating previously untreated mantle cell lymphoma. Acalabrutinib and umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Ublituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib and umbralisib with ublituximab may work better in treating mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate After Induction (Six Cycles)

  Defined as the proportion of response-evaluable participants that achieve a CR at the end of the induction therapy. CR rate after the induction therapy was estimated by the proportion of response-evaluable patients achieving CR after the induction therapy, along with the 95% exact binomial confidence interval.

  Participants were assessed at the end of the induction therapy (24 weeks post-baseline). The induction therapy included six 28-day cycles of the study treatment.

Secondary Outcomes (1)

• Overall Response Rate (ORR)

  Participants were followed up to 24 months after the end of protocol therapy.

Study Arms (1)

Treatment (ublituximab, acalabrutinib, umbralisib)

EXPERIMENTAL

Patients receive ublituximab IV over 90 minutes-4 hours on days 1, 8, and 15 of cycle 1 and days 1 of cycles 2-6. Patients also receive acalabrutinib PO BID and umbralisib PO QD on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive ublituximab IV on day 1 on cycles 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30. Patients also receive acalabrutinib Po BID and umbralisib PO QD on day 1-28. Treatment repeats every 28 days for 24 cycles in the absence of disease progression of unacceptable toxicity.

Drug: Acalabrutinib; Biological: Ublituximab; Drug: Umbralisib

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Treatment (ublituximab, acalabrutinib, umbralisib)

Ublituximab BIOLOGICAL

Given IV

Also known as: LFB-R603, TG-1101, TG-20, TGTX-1101

Treatment (ublituximab, acalabrutinib, umbralisib)

Umbralisib DRUG

Given PO

Also known as: 2-((1S)-1-(4-Amino-3-(3-fluoro-4-(1-methylethoxy)phenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-1-benzopyran-4-one, RP-5264, RP5264, TGR-1202

Treatment (ublituximab, acalabrutinib, umbralisib)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Histologically confirmed mantle cell lymphoma with documentation of monoclonal CD20+ B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
• Age \>= 65 years; or \>= 50 years and deemed ineligible for aggressive induction therapy or autologous stem cell transplant by the investigator, or unwilling to undergo aggressive induction; or \>= 18 years with documented del(17p), or TP53 mutation, or complex karyotype (CK) by cytogenetics and/or fluorescence in situ hybridization (FISH) studies
• Requiring treatment for MCL, and for which no prior systemic anticancer therapies have been received (local radiotherapy not exceeding a total dose of 20 Gy at least 2 weeks prior the first dose of study therapy is allowed)
• Measurable disease by computed tomography (CT) or positron emission tomography (PET)/CT scan with one or more sites of disease \>= 1.5 cm in longest dimension (including splenomegaly), or bone marrow involvement with or without malignant lymphocytosis
• Without bone marrow involvement: Absolute neutrophil count (ANC) \>= 1000/mm\^3
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• With bone marrow involvement: ANC \>= 500/mm\^3
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• Without bone marrow involvement: Platelets \>= 75,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
• With bone marrow involvement: Platelets \>= 30,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) or =\< 3X ULN for Gilbert's disease

You may not qualify if:

• Chronic use of corticosteroids \>= 20 mg/day (short-term use of steroids \< 14 days is allowed)
• Major surgical procedure within 28 days of start of protocol therapy. 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
• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
• Concurrent participation in another therapeutic clinical trial
• Subjects for whom the goal of therapy is tumor debulking before stem cell transplant
• History of prior malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for \>= 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
• 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
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
• 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
• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
• Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
• History of significant cerebrovascular disease/event, including stroke, myocardial infarction or intracranial hemorrhage, within 6 months prior to start of protocol therapy
• Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib; ublituximab; LFB-R603; umbralisib

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

Results Point of Contact

• Title: Dr. Alexey Danilov
• Organization: City of Hope Medical Center

adanilov@coh.org

626-359-8111

Study Officials

• Alexey V Danilov

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 5, 2021
• Study Start: March 26, 2021
• Primary Completion: July 31, 2022
• Study Completion: September 20, 2025
• Last Updated: December 2, 2024
• Results First Posted: November 18, 2023

Record last verified: 2024-11

Locations

US (1)