Copanlisib Plus Venetoclax in R/R DLBCL

NCT04572763 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-069
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is evaluating the combination of two drugs, copanlisib and venetoclax, as a possible treatment for trelapsed/refractory diffuse large B-cell lymphoma (DLBCL) The names of the study drugs involved in this study are:

• Copanlisib
• Venetoclax

Conditions

Diffuse Large B Cell Lymphoma; Relapsed Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Keywords

Diffuse Large B Cell Lymphoma; Relapsed Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of venetoclax in combination with copanlisib (recommended phase II dose (RP2D) - Phase 1

  The highest dose of the drug combination that does not cause unacceptable side effects as assessed by protocol-specified DLT criteria.

  28 Days up to 1 year

• Overall response rate (ORR) - Phase II

  Defined as the partial response (PR) and complete response (CR) rate, according to the Lugano criteria.

  28 Days

Secondary Outcomes (6)

• Partial response Rate (PR)

  28 Days

• Complete response Rate (CR)

  28 Days

• Duration of response (DOR)

  Every 3 months to 1 year

• Progression-free survival (PFS)

  Time from randomization (or registration) to the date of first documented progression or date of death from any cause, whichever comes first, for up to 5 years.

• Overall survival (OS)

  Time from randomization (or registration) to the date of death from any cause, assessed for up to 5 years.

Study Arms (2)

Dose Escalation Copanlisib + Venetoclax

EXPERIMENTAL

Phase 1 * Dose escalation will occur using a 3+3 design * Copanlisib will be administered IV on days 1, 8 and 15 in 28 day cycle * Venetoclax will be administered orally daily for each 28-day cycle. During cycle 1, a venetoclax dose ramp-up is performed in the outpatient setting

Drug: Copanlisib; Drug: Venetoclax

Recommended phase II dose (RP2D) Copanlisib + Venetoclax

EXPERIMENTAL

Patients will be treated with copanlisib in combination with venetoclax, administered at the Recommended phase II dose (RP2D).

Drug: Copanlisib; Drug: Venetoclax

Interventions

Copanlisib DRUG

Intravenous infusion

Also known as: Aliqopa

Dose Escalation Copanlisib + Venetoclax; Recommended phase II dose (RP2D) Copanlisib + Venetoclax

Venetoclax DRUG

Tablet taken orally

Also known as: Venclexta

Dose Escalation Copanlisib + Venetoclax; Recommended phase II dose (RP2D) Copanlisib + Venetoclax

Eligibility Criteria

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

You may qualify if:

• A confirmed diagnosis of DLBCL according to the 2016 WHO classification. Patients with high-grade B-cell lymphoma with translocations of MYC and BCL-2 and/or BCL-6 are eligible
• Relapsed after autologous stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy or not a candidate for these therapies
• Willingness to undergo a pre-treatment biopsy. If considered unsafe to proceed with biopsy, archival tissue samples may be utilized after discussion with the PI. Archival samples performed within 90 days and without intervening therapy are also acceptable if they meet the criteria as specified in the laboratory manual.
• ECOG performance status \< 2
• Age ≥ 18 years
• Patients must meet the following hematologic criteria at screening:
• Absolute neutrophil count ≥1000 cells/mm3 (0.5 x 109/L), with no white-blood cell growth factor use for at least 7 days prior to screening.
• Platelet count ≥75,000 cells/mm3 (75 x 109/L) or ≥50,000 cells/mm3 (50 x 109/L if documented disease involvement of the bone marrow), without platelet transfusion within 7 days of screening
• Hemoglobin (Hb) ≥ 8 g/dL, without blood transfusion within 7 days of screening
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement by lymphoma)
• Lipase ≤ 1.5 x ULN
• Total bilirubin ≤ 1.5 x ULN (\< 3 x ULN for patients with Gilbert's syndrome, patients with cholestasis due to compressive adenopathies of the hepatic hilum or documented liver involvement or with biliary obstruction due to lymphoma)
• Adequate renal function defined by serum creatinine ≤1.5 x ULN or creatinine clearance (by Cockroft-Gault) ≥ 50 ml/min
• Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and 6 months for WOCBP and for men after the last administration of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control, e.g. intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, use of two forms of birth control, and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) within 2 weeks of Cycle 1/Day 1 with the following exceptions:
• Limited palliative radiation is allowed if completed \> 1 week of C1D1
• Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone is allowed until C1D1.
• Chronic systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent.
• History of other malignancies, except:
• Malignancy treated medically or surgically with curative intent and with no known active disease present for ≥2 years before the first dose of study drug
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease.
• Localized prostate cancer and low-risk prostate cancer on active surveillance
• Within three months of autologous stem cell transplantation at time of starting study treatment
• Within six months of allogeneic stem cell transplantation at time of starting study treatment or active graft vs. host disease requiring systemic treatment or prophylaxis within 6 weeks of starting study treatment
• Vaccinated with live, attenuated vaccines of any kind \<4 weeks before first dose of study drug
• History of or active autoimmune disease requiring systemic immunosuppression
• Recent infection requiring intravenous antibiotics that was completed ≤7 days before the first dose of study drug, or any uncontrolled active systemic infection
• Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not included on the list of prohibited medications

Sponsors & Collaborators

• AbbVie: collaborator
• Bayer: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (3)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

copanlisib; venetoclax

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

Study Officials

• Jennifer Crombie, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: October 1, 2020
• Study Start: September 8, 2021
• Primary Completion: July 29, 2025
• Study Completion (Estimated): July 29, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)