Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma

NCT02242097 | Active Not Recruiting Phase 2 Results DMC

• 5 other identifiers: NU 14H06NCI-2014-01777PCI-32765MCL2003STU00098385P30CA060553
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being done to see whether or not a drug called ibrutinib can be given to patients with mantle cell lymphoma (MCL) as maintenance therapy after induction chemotherapy. This drug blocks an enzyme that affects how the lymphocytes grow and survive. The investigators hope to learn how safe and effective ibrutinib is for treating patients with MCL after responding to induction chemotherapy.

Conditions

Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Determine the Progression-free Survival (PFS) Rate After 3 Years

  PFS will be measured from start of treatment to time of progression. Evidence of clinical progression will be documented by imaging (CT scan) for patients who have measurable disease. Progression is defined using the LUGANO Criteria, as a Deauville score of 4 or 5 (increased uptake compared to baseline) or the appearance of new lesions

  Assessed at 3 years

Secondary Outcomes (3)

• Incidence of Adverse Events, Defined According to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.0

  Up to 30 days after completion of study treatment, maximum 4 years post-first dose

• Rate of Conversion From Partial Response (PR) to Complete Response (CR)

  Up to 4 years

• Overall Survival (OS) After 4 Years

  Up to 4 years post-first dose

Other Outcomes (1)

• Compare Minimum Residual Disease (MRD) Results Overtime by Polymerase Chain Reaction (PCR) and Correlate These With PFS and OS

  Four time-points: baseline (pre-treatment), after 1 month and 6 months of treatment, and approximately 18-24 months post-first dose of treatment

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib orally PO QD on days 1-28. Courses repeat every 28 days for up to 4 years in the absence of disease progression, unacceptable toxicity, or patient preference.

Drug: ibrutinib; Other: laboratory biomarker analysis

Interventions

ibrutinib DRUG

Given PO

Also known as: Bruton's tyrosine kinase inhibitor PCI-32765, BTK inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (ibrutinib)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed mantle cell lymphoma (MCL)
• Please note: Measurable disease is not required, but will be followed if it exists
• Patients must have received 4 or more cycles of one of the following prior systemic induction chemotherapy regimens:
• Rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), prednisone (R-CHOP) (with or without alternating rituximab, dexamethasone, cytarabine \[ara-c\], cisplatin \[platinum\] \[R-DHAP\]) with or without autologous (auto) stem cell transplant (SCT)
• Hyper-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (adriamycin), dexamethasone (CVAD) with or without auto SCT
• Bendamustine + rituximab with or without auto SCT
• Please note:
• Patients who received combinations of the above regimens are not eligible for enrollment
• At the time of registration, patients must be at least 14 days out from last dose of cytotoxic chemotherapy, but no more than 90 days; if a patient underwent auto SCT, he/she must demonstrate engraftment (per treating investigator's discretion) and must meet all other hematological requirements as outlined below
• Patients must have achieved a response to induction chemotherapy (either CR or PR by Cheson 2007 criteria) and be without known progression
• Patients may have received prior radiotherapy
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Absolute neutrophil count (ANC) \>= 1000/mm\^3, independent of growth factor support
• Platelets \>= 100,000/mm\^3, or \>= 50,000 in cases of ongoing bone marrow involvement (in either case, these must be independent of transfusion support)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)

You may not qualify if:

• Patients who have received \>= 7 days of prior ibrutinib or any prior treatment with another Bruton tyrosine kinase (BTK) inhibitor are not eligible
• Patients receiving ongoing treatment with any other investigational agents are not eligible
• Patients receiving live/attenuated vaccinations within 4 weeks prior to registration are not eligible
• Patients with a known central nervous system (CNS) involvement of lymphoma are not eligible (CNS staging not required)
• Patients who have undergone major surgery within 4 weeks prior to registration are not eligible
• Patients diagnosed or treated for malignancy other than MCL are not eligible unless they meet one of the following exceptions:
• Malignancy treated with curative intent and with no known active disease present for \>= 3 years before registration and felt to be at low risk for recurrence by the treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Patients with a history of stroke or intracranial hemorrhage within 6 months prior to registration are not eligible
• Patients who require anticoagulation with warfarin or equivalent vitamin K antagonists are not eligible
• Patients who require chronic treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors are not eligible
• NOTE: Patients who are currently on treatment with strong CYP3A4/5 inhibitors may be eligible if they are able to be switched to an alternative therapy that is not a strong CYP3A4/5 inhibitor prior to registration on study
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib are not eligible
• Patients with uncontrolled intercurrent illness including, but not limited to, any of the following are not eligible:

Sponsors & Collaborators

• Northwestern University: lead
• Janssen Scientific Affairs, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Karmali R, Abramson JS, Stephens DM, Barnes J, Winter JN, Ma S, Gao J, Kaplan J, Petrich AM, Hochberg E, Takvorian T, Mi X, Nelson V, Gordon LI, Pro B. Ibrutinib maintenance after frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 Dec 12;7(23):7361-7368. doi: 10.1182/bloodadvances.2023011271.

  PMID: 37756532 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib

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. Reem Karmali
• Organization: Northwestern University, Feinberg School of Medicine

reem.karmali@northwestern.edu

(312) 695-0990

Study Officials

• Barbara Pro, MD

  Northwestern University

  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: September 12, 2014
• First Posted: September 16, 2014
• Study Start: January 12, 2015
• Primary Completion: January 5, 2023
• Study Completion: January 1, 2025
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-02

Locations

US (5)