Copanlisib and Nivolumab in Treating Patients With Richter's Transformation or Transformed Indolent Non-Hodgkin Lymphoma

NCT03884998 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 20066NCI-2018-01880STUDY00018655P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the best dose and how well copanlisib when given together with nivolumab works in treating patients with Richter's transformation or transformed indolent non-Hodgkin lymphoma. Copanlisib 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 and nivolumab may work better in treating patients with Richter's transformation or transformed non-Hodgkin lymphoma.

Conditions

Marginal Zone Lymphoma; Richter Syndrome; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Indolent Non-Hodgkin Lymphoma; Lymphoplasmacytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities of copanlisib in combination with nivolumab

  Will be summarized for the safety population by dose level. All adverse events (AEs) will be coded by system organ class, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, and severity grade using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.

  Up to day 28

• Incidence of adverse events

  Will be assessed by CTCAE v5. All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.

  Up to 48 weeks

Secondary Outcomes (3)

• Overall response rate (ORR) or complete response (CR) + partial response (PR)

  Up to 48 weeks

• Duration of response

  Up to 48 weeks

• Progression-free survival (PFS)

  Up to 48 weeks

Other Outcomes (2)

• Tumor response

  Up to 48 weeks

• Evaluation of T-cell repertoire of patients with transformed chronic lymphocytic leukemia (CLL)/non-Hodgkin's lymphoma (NHL) after receiving nivolumab

  Up to 48 weeks

Study Arms (1)

Treatment (copanlisib and nivolumab)

EXPERIMENTAL

Patients receive copanlisib IV over 60 minutes on days 1, 8, and 15 and nivolumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Biological: Nivolumab

Interventions

Copanlisib DRUG

Given IV

Also known as: BAY 80-6946, PI3K Inhibitor BAY 80-6946

Treatment (copanlisib and nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (copanlisib and nivolumab)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Richter syndrome (RS; transformed CLL), or indolent NHL (follicular lymphoma \[FL\], lymphoplasmacytic lymphoma \[LPL\], marginal zone lymphoma \[MZL\]) in transformation. Only patients who have diffuse large B-cell lymphoma (DLBCL) histology are eligible in transformation are eligible (for example, patients with transformation into Hodgkin lymphoma subtype are not eligible).
• Participants with RS must have received at least 2 cycles of prior systemic therapy for either RS or underlying CLL.
• Participants with FL and other indolent lymphomas in transformation must have underwent \>= 1 prior chemo-immunotherapy regimen (e.g., rituximab/cyclophosphamide/doxorubicin/prednisone/vincristine \[R-CHOP\] or similar) administered for \>= 2 cycles and have had either documented disease progression to the most recent treatment regimen, or refractory disease and must not be candidates for or planning to pursue autologous stem cell transplant, or must have relapsed following autologous stem cell transplant which took place at least 3 months prior to study therapy.
• Radiographically measurable lymphadenopathy (\>= 1.5 cm) or measurable extra-nodal disease.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2.
• Total bilirubin =\< 2 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x institutional ULN.
• Estimated creatinine clearance (CrCL) using the Cockroft-Gault equation \>= 30 mL/min.
• Platelets \>= 75,000/mm\^3 (\>= 25,000/mm\^3 if due to disease involvement in the bone marrow; transfusion is not permitted to achieve this level).
• Absolute neutrophil count \>= 1000/mm\^3 (\>= 500/mm\^3 if due to disease involvement in the bone marrow).
• Female participants who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile (i.e. tubal ligation), OR
• Participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin at screening and:
• Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing the informed consent through 1 month after the last dose of copanlisib, or 5 months after the last dose of nivolumab, whichever is later, or

You may not qualify if:

• History of allogeneic bone marrow or organ transplant.
• Prior therapeutic intervention with any of the following:
• Therapeutic anti-cancer antibodies within 2 weeks.
• Radio- or toxin-immunoconjugates within 10 weeks.
• Radiation therapy within 2 weeks.
• All other chemotherapy within 3 weeks prior to initiation of study therapy.
• Targeted therapy - within 6 half-lives (for example, 36 hours for ibrutinib).
• History of prior malignancy except:
• Malignancy treated with curative intent and no known active disease present for \>= 2 years prior to initiation of therapy on current study.
• 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.
• Any adverse event related to prior therapy that has not recovered to =\< grade 1 (excluding grade 2 alopecia and grade 2 neuropathy).
• Chronic use of corticosteroids in doses which exceed 15 mg of prednisone per day, or the equivalent.
• Uncontrolled immune hemolysis or thrombocytopenia.

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

copanlisib; Nivolumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

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

Study Officials

• Alexey V Danilov

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 21, 2019
• Study Start: February 26, 2019
• Primary Completion (Estimated): November 4, 2026
• Study Completion (Estimated): November 4, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

US (3)