Bendamustine + Obinutuzumab Induction With Obinutuzumab Maintenance in Untreated Mantle Cell Lymphoma

NCT03311126 | Terminated Phase 2 Results DMC FDA Drug

• 6 other identifiers: UW160862017-0609NCI-2017-01729A534260SMPH\MEDICINE\HEM-ONCProtocol Version 11/18/2019
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II single-arm, open-label, multicenter study evaluating the efficacy and safety of the combination of induction chemoimmunotherapy with bendamustine and obinutuzumab (BO) followed by consolidation therapy and maintenance therapy with obinutuzumab in subjects who have not received prior cytotoxic chemotherapy for their Mantle Cell Lymphoma (MCL) (i.e., prior single agent rituximab is permitted, prior involved-field radiotherapy is permitted).

Conditions

Mantle Cell Lymphoma; Non-hodgkin Lymphoma; Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) at 2 Years

  For each patient, progression-free survival (PFS) is measured from cycle 1 day 1 (C1D1) of induction chemoimmunotherapy to the day patient experiences an event of disease progression or death, whichever occurs first. If a patient has not experienced an event at the time of analysis, patient's data will be censored at the date of the last available evaluation. The 2-year PFS probability will be estimated using the Kaplan-Meier method. From the date of C1D1 of induction therapy to the date of progression or death; in the absence of progression or death, participants will be followed for a minimum of 24 months after completion of study-related treatment. PFS rates at 2 years are reported here.

  Up to 2 years

Secondary Outcomes (5)

• Minimal Residual Disease (MRD) Status

  At the end of Cycle 2 of induction therapy (each cycle is 28 days), following consolidation phase (after 6 cycles of induction, consolidation is 4 weekly doses of obinutuzumab), within 30 days of completing protocol therapy (up to 15 months total)

• Estimate the Concordance Rate Between Peripheral Blood (PB) and Bone Marrow Aspirates (BMA) in Predicting MRD Status.

  At the end of Cycle 2 of induction therapy (each cycle is 28 days), following consolidation phase of therapy (after 6 cycles of induction, consolidation is 4 weekly doses of obinutuzumab), and within 30 days of completing protocol therapy

• Determine Objective Response Rates (CR + PR) With Induction Bendamustine and Obinutuzumab (BO) in Previously Untreated MCL Using the Lugano Classification for Response in Lymphoma

  Assessed up to cycle 8 of maintenance therapy, up to 15 months on study

• Overall Survival (OS)

  Up to 3 years

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 During Therapy Induction BO Chemoimmunotherapy and Obinutuzumab Consolidation and Maintenance

  Up to 25 months (until 30 days after completion of final dose of study-related treatment)

Study Arms (1)

Bendamustine + Obinutuzumab (BO)

EXPERIMENTAL

Induction chemoimmunotherapy (28 day cycles): Bendamustine 90 mg/m2 IV days 1 \& 2 every 28 days X 4-6 cycles Obinutuzumab: * Cycle 1: 100 mg IV day 1, 900 mg IV day 2, 1000 mg IV days 8 \& 15 * Cycles 2-6: 1000 mg IV day 1 Consolidation phase: Obinutuzumab 1000 mg IV weekly X 4 doses Maintenance phase (8 week cycles): Obinutuzumab 1000 mg IV on day 1 of cycles 1-8

Drug: Bendamustine; Drug: Obinutuzumab

Interventions

Bendamustine DRUG

Bendamustine is a chemotherapeutic agent that has dual functional properties of both an alkylating agent and a nitrogen mustard. Through these unique cytostatic properties, bendamustine is able to inhibit DNA transcription, replication, and repair. Bendamustine is approved in the U.S. for treatment of chronic lymphocytic leukemia (CLL) and for indolent B cell non-Hodgkin lymphomas (NHLs) progressing during or within 6 months of rituximab or a rituximab - containing regimen.

Bendamustine + Obinutuzumab (BO)

Obinutuzumab DRUG

Obinutuzumab is a glycoengineered, humanized, type II anti-CD20 monoclonal antibody (mAb).

Also known as: GA101, RO5072759

Bendamustine + Obinutuzumab (BO)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years at the time of signing the informed consent document.
• Histologically confirmed mantle cell lymphoma (confirmation of cyclin D1 positivity on diagnostic biopsy).
• Subjects must have at least one bi-dimensionally measurable lesion; one of the measurements must be ≥1.5 cm in one direction
• No prior cytotoxic chemotherapy; prior therapy with single-agent rituximab is permitted. Prior involved-field radiotherapy to symptomatic nodal sites of involvement is also permitted.
• Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease.
• Must meet one of the following criteria:
• Not eligible for more intensive cytotoxic chemotherapy or consolidative autologous stem cell transplant based on one or more of the following:
• Clinically significant heart or lung comorbidities, as reflected by at least 1 of the following:
• Left ventricular ejection fraction (LVEF) ≤ 50%
• Chronic stable angina or congestive heart failure controlled with medication
• New York Heart Association (NYHA) class III or IV heart failure
• Symptomatic chronic pulmonary disease or requirement for intermittent or continuous oxygen therapy
• Presence of other medical comorbidity or limitation in functional status which the investigator judges to be incompatible with an acceptable risk to the subject with the use of intensive chemotherapy. The associated comorbidity or functional limitation must be clearly documented in the medical record at the time of enrollment.
• Subject has been informed of the risks and benefits of intensive chemotherapy and autologous stem cell transplant for treatment of mantle cell lymphoma and has refused this option. This discussion must be clearly documented in the medical record at the time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 at study entry.

You may not qualify if:

• Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.
• Concurrent use of other anti-cancer agents or treatments.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment.
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years.
• Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other mAb therapy.
• Known to be positive for HIV or infectious hepatitis (type B or C).
• Pregnant or breast-feeding females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center home page

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Julie Chang, MD
• Organization: University of Wisconsin Carbone Cancer Center

jc2@medicine.wisc.edu

(608) 263-9823

Study Officials

• Julie Chang, MD

  University of Wisconsin, Madison

  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 28, 2017
• First Posted: October 16, 2017
• Study Start: September 29, 2017
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)