Copanlisib Hydrochloride and Nivolumab in Treating Patients With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

NCT03484819 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: NCI-2018-00478MC178710193UM1CA186686UM1CA186709
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 15

Brief Summary

This phase II trial studies how well copanlisib hydrochloride and nivolumab work in treating patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma that has come back (recurrent) or does not responded to the treatment (refractory). Copanlisib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving copanlisib hydrochloride and nivolumab may work better in treating patients with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma compared to standard of care.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Will be estimated by the number of successes divided by the total number of evaluable patients. A success is defined as a patient that reports a confirmed complete or partial response according to Lugano criteria.

  23 months

Secondary Outcomes (4)

• Number of Grade 3+ Adverse Events

  24 months

• Progression Free Survival

  12 months

• Duration of Response (DOR)

  12 months

• Overall Survival Time

  24 months

Other Outcomes (1)

• Lymph3Cx Cell-of-Origin (COO) Molecular Subtyping Assay for Primary Mediastinal B Cell Lymphoma (PMBCL) and Diffuse Large B Cell Lymphoma (DLBCL) Subtypes

  Up to 5.5 years

Study Arms (1)

Treatment (copanlisib hydrochloride, nivolumab)

EXPERIMENTAL

Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8 and 15 of cycles 1-8 and days 1 and 15 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-8 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib Hydrochloride; Biological: Nivolumab

Interventions

Copanlisib Hydrochloride DRUG

Given IV

Also known as: 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride

Treatment (copanlisib hydrochloride, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (copanlisib hydrochloride, nivolumab)

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 a histopathologically confirmed diagnosis of diffuse large B-cell lymphoma (DBLCL) or primary mediastinal large B-cell lymphoma
• Patients must have measurable disease, defined as at least one lesion that is \>= 15 mm (\>= 1.5 cm) in the longest axis on cross-sectional imaging and measurable in two perpendicular dimensions per spiral computed tomography (CT) scan or positron-emission tomography (PET)-CT scan
• Patients must have disease that is recurrent or refractory to standard therapy; patients must have failed front-line therapy and declined or are not candidates for autologous stem cell transplant (ASCT) or have failed prior ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy of greater than 12 weeks
• White blood cell (WBC) \>= 2000/mm\^3
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \> 9.0 g/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Aspartate transaminase (AST) =\< 2.5 x ULN
• Serum creatinine =\< 2.0 mg/dL OR calculated creatinine clearance (CrCl) \>= 30 mL/min (if using the Cockcroft-Gault formula)
• Negative urine or serum pregnancy test for females of child bearing potential within 7 days prior to registration
• The effects of copanlisib and nivolumab on the developing human fetus are unknown; for this reason, and because the study drugs used in this trial are known to be teratogenic, females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 5 months after the last dose of study drug; males who are the sexual partners of a female of child-bearing potential must use any contraceptive method with a failure rate of less than 1% per year for the duration of study participation and for a period of 7 months after the last dose of study drug; these periods of required use of contraception have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that females of child-bearing potential use contraception for 5 months and males who are the sexual partners of females of child-bearing potential use contraception for 7 months
• Females must not be breast-feeding for 1 month after last dose

You may not qualify if:

• Any high grade B-cell lymphoma
• Patients who have had chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C), anticancer antibodies within 4 weeks, radio or toxin immunoconjugates within 2 weeks, radiation therapy within 3 weeks or major surgery within 2 weeks prior to entering the study
• Palliative (limited-field) radiation therapy is permitted if the patient has additional measurable lesions to assess response of therapy
• Patients who have not recovered to grade 1 or less from any adverse events due to agents administered more than 4 weeks earlier (excluding alopecia)
• Patients who are receiving any other investigational agents
• Patients should be excluded if they have had prior treatment with a Pi3 kinase inhibitor, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; Note: Patients who previously received CART therapy and progressed will be eligible
• Patients who have received autologous stem cell transplant (ASCT) =\< 8 weeks prior to the first dose of study drug or no adequate count recovery
• Patients with a prior history of allogeneic stem cell or solid organ transplantation
• Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on magnetic resonance imaging (MRI) obtained within 4 weeks of registration or progressive neurological decline; patients with primary central nervous system (CNS) lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment; similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib and/or nivolumab
• History of severe hypersensitivity reaction to any monoclonal antibody
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, non-healing wound or ulcer, or bone fracture, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, known history of atrial fibrillation except those with 1 event that has resolved more than 1 year ago without recurrence, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because copanlisib and nivolumab are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with copanlisib or nivolumab, breastfeeding should be discontinued for 1 month after last dose if the mother is treated with copanlisib or nivolumab
• Patients with human immunodeficiency virus (HIV):

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (15)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

HaysMed

Hays, Kansas, 67601, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

Location

Ascension Via Christi - Pittsburg

Pittsburg, Kansas, 66762, United States

Location

Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University Health Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

copanlisib; Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nora Bennani, M.D.
• Organization: Mayo Clinic

bennani.nora@mayo.edu

(507) 284-2511

Study Officials

• Nabila N Bennani

  Mayo Clinic Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 2, 2018
• Study Start: December 13, 2019
• Primary Completion: November 18, 2022
• Study Completion: August 14, 2024
• Last Updated: March 3, 2025
• Results First Posted: January 23, 2024

Record last verified: 2025-02

Locations

US (15)