Obinutuzumab in Combination With Ibrutinib in Treating Patients With Relapsed Mantle Cell Lymphoma

NCT02736617 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY00015255NCI-2016-00398
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well obinutuzumab works in combination with ibrutinib in treating patients with mantle cell lymphoma that has returned (relapsed) or that does not respond to treatment (refractory). Obinutuzumab binds to a protein called cluster of differentiation (CD)20, which is found on B cells and some types of leukemia and lymphoma cells and help the immune system kill cancer cells. Ibrutinib blocks a protein called Bruton's tyrosine kinase (BTK), which may help keep cancer cells from growing. Giving obinutuzumab in combination with ibrutinib may kill more cancer cells.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Best Overall Objective Response or Complete Response/Partial Response (CR/PR)

  Overall response is measured combining bone marrow biopsy with CT or PET, measuring target and evaluable non-targeted lesions, according to the Lugano criteria. For FDG-PET, the Deauville criteria is used in conjecture with CT to assess lesion FDG-update. Deauville scale ranges from 1 to 5, where 1 is best (no uptake or no residual uptake) and 5 is worst (markedly increased uptake or any new lesion). If bone marrow is involved prior to treatment, infiltrate must have cleared on repeat biopsy for CR; bone marrow assessment is irrelevant for determination of PR. Measurements are taken at baseline, end of cycle 2, end of induction (after cycle 6) and every 4 months thereafter. Best overall response is any CR or PR reported since start of therapy. Percent of participants with complete response or partial response (CR+PR) are reported along with 95% confidence interval.

  From first dose of study therapy until the 6-month disease assessment (Cycle 6, Day1 or End of Induction Day 28). Disease assessment is also assessed at end of Cycle 2 (2-months).

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  Time from the first day of combined study treatment to disease progression or death, whichever occurs first, assessed up to approximately 4 years, 11 months, after first dose of study drug(s)

• Number of Participants With Treatment-related Toxicities, Grade 3 or Higher, as Assessed by CTCAE v4.0

  Measured from the first dose of either study drug until 30 days after the last dose of study drug, for approximately 4 years, 11 months.

Study Arms (1)

Treatment (obinutuzumab and ibrutinib)

EXPERIMENTAL

Patients receive obinutuzumab IV over 30 minutes on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-6. Patients also receive ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have PR continue to receive obinutuzumab IV every 2 months and ibrutinib PO QD for 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Biological: Obinutuzumab

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (obinutuzumab and ibrutinib)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (obinutuzumab and ibrutinib)

Eligibility Criteria

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

You may qualify if:

• Subjects must have a diagnosis of relapsed or refractory mantle cell lymphoma as follows:
• Diagnosis of mantle cell lymphoma (MCL) must include morphology and expression of either cyclin D1 in association with other relevant markers (eg, CD19, CD20, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
• Relapsed or refractory disease is defined as no response or progressive disease to prior treatment if the prior treatment comprised any of the following:
• regimen containing an anti-CD20 antibody administered for \>= 2 doses, and/or
• \>= 1 regimen containing 1 cytotoxic agent (e.g., bendamustine, chlorambucil, cyclophosphamide, cytarabine, doxorubicin) administered for 2 cycles
• At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma (Cheson Criteria); the site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count (ANC) \>= 1.0 K/cu mm; for subjects with ANC \< 1.0 K/cu mm due to significant marrow involvement by MCL, ANC must be \> .5 K/cu mm
• Platelets (plt) \>= 50 K/cu mm; for subjects with plt \< 50 K/cu mm due to significant marrow involvement by MCL, plt must be \> 25 K/cu mm
• Total bilirubin =\< 2.5 X institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
• Creatinine =\< 2
• Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for females, these restrictions apply for 18 months after last dose of obinutuzumab, or 1 month after the last dose of ibrutinib, whichever is later; for males, these restrictions apply for 180 days after the last dose of obinutuzumab or 3 months after the last dose of ibrutinib, whichever is later
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Major surgery within 4 weeks of drug administration
• Diagnosed or treated for malignancy other than MCL, except:
• Malignancy treated with curative intent and with no known active disease present for \>= 2 years
• Adequately treated non-melanoma skin cancer or melanoma in situ without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Asymptomatic prostate cancer managed with "active surveillance"
• Localized prostate cancer treated with definitive treatment including radiation or surgery. Patients on adjuvant hormone deprivation treatment such as lupron are eligible. Patients with known metastatic disease are ineligible
• History of stroke or intracranial hemorrhage within 6 months prior to randomization
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon)
• Vaccinated with live, attenuated vaccines within 4 weeks of randomization
• Requires treatment with strong cytochrome P450 3A (CYP3A) inhibitors
• Subjects who have had standard cytotoxic chemotherapy or radiotherapy within 3 weeks prior to entering the study or those whose adverse events due to agents administered more than 3 weeks earlier have not recovered to =\< grade 1; this excludes alopecia and hematologic adverse events
• Subjects who have had radiotherapy within 2 weeks prior to entering the study or those whose adverse events due to radiotherapy more than 2 weeks earlier have not recovered to =\< grade 1
• Subjects who have received investigational or approved oral or "targeted" agents (such as spleen tyrosine kinase \[SYK\], phosphatidylinositol 3 kinase \[PI3K\], B-cell chronic lymphocytic leukemia \[CLL\]/lymphoma 2 \[bcl-2\], BTK inhibitors) or lenalidomide within 1 week prior to entering the study or those whose adverse events due to agents administered more than 1 week earlier have not recovered to =\< grade 1; this excludes hematologic adverse events; the exception is subjects who are currently receiving ibrutinib (for \< 14 days). In this case, ibrutinib can be continued
• Subjects who have received monoclonal antibodies (such as Rituxan) within 1 week prior to entering the study or those whose adverse events due to agents administered more than 1 week earlier have not recovered to =\< grade 1; this excludes hematologic adverse events

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Genentech, Inc.: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; 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

Limitations and Caveats

Study was powered to detect an 85% response rate compared to a 55% control rate. Simon's Two-Stage design planned to enroll 6 at Stage 1; if 4 or more achieved CR/PR then an additional 14 would be enrolled in Stage 2 for a total of 20 participants. Study satisfied Stage 1 requirements but lagging enrollment caused study to close with only 10 participants enrolled. Of the 10 only 9 were efficacy evaluable. Power: P(x\>=8\|n=9, p=0.85) = 0.599; x=success, n=evaluable, p=expected probability

Results Point of Contact

• Title: Dr. Stephen E. Spurgeon, Associate Professor of Medicine
• Organization: Oregon Health and Sciences University, Knight Cancer Institute

spurgeos@ohsu.edu

503-494-8950

Study Officials

• Stephen E Spurgeon

  OHSU Knight Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 13, 2016
• Study Start: July 5, 2016
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: January 5, 2022
• Results First Posted: January 5, 2022

Record last verified: 2021-12

Locations

US (1)