Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

NCT04939272 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22043NCI-2021-03219P30CA033572
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects, best dose, and effectiveness of copanlisib and venetoclax in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving copanlisib and venetoclax may help treat patients with mantle cell lymphoma.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (Phase I)

  Toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to end of cycle 2 (1 cycle = 28 days)

• Overall response rate (Phase II)

  Defined as the proportion of response-evaluable participants that achieve a best response of either complete response (CR) or partial response (PR) during protocol therapy. Will be estimated along with the 2-sided 95% exact binomial confidence interval.

  Up to 2 years

Secondary Outcomes (6)

• Duration of response

  Time from the first achievement of PR or CR to time of progressive disease, start of non-protocol anti-lymphoma therapy, or death, whichever earlier, assessed up to 2 years

• Progression-free survival

  From start of protocol treatment to time of disease relapse/progression, or death due to any cause, whichever occurs earlier, assessed up to 2 years

• Overall survival

  From start of protocol treatment to time of death due to any cause, assessed up to 2 years

• Incidence of adverse events

  Up to 90 days after completion of treatment

• Plasma pharmacokinetics (PK) of copanlisib (Cmax)

  From 30 minute before Copanlisib on cycle 2 day 15 through 24 hours after (Each cycle is 28 days)

Study Arms (1)

Treatment (copanlisib hydrochloride, venetoclax)

EXPERIMENTAL

Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15, and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level. Venetoclax will have a weekly dose ramp up from 20mg, 50mg, 100mg, 200mg, and then 400mg thereafter.

Drug: Copanlisib Hydrochloride; Drug: Venetoclax

Interventions

Copanlisib Hydrochloride DRUG

Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 for each cycle. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level.

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, venetoclax)

Venetoclax DRUG

Patients receive venetoclax PO QD on days 1-28 for each cycle. Venetoclax will have a weekly dose ramp up in cycle one from 20mg, 50mg, 100mg, 200mg, and then 400mg daily thereafter starting from cycle 2.

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (copanlisib hydrochloride, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Life expectancy \>= 3 months (per physician assessment)
• Ability to take oral medication
• Pathologically confirmed MCL, with documentation of monoclonal B cells showing one of the following:
• Overexpression of cyclin D1 in association with other relevant markers (e.g., CD19, CD20, PAX5, CD5), OR
• Chromosomal translocation t(11;14)(q13; q32), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
• Documented failure to achieve at least partial response (PR) with, or documented disease progression after the most recent treatment regimen
• At least 1 prior treatment regimen for MCL which either included chemo-immunotherapy or a targeted agent (i.e., ibrutinib) administered for at least 2 cycles
• Have radiologically measurable lymphadenopathy or extranodal lesion, (defined as \>= 1 lesion that measures \>= 2.0 cm in the longest diameter), or splenomegaly, or bone marrow involvement with or without malignant lymphocytosis
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 without bone marrow involvement or ANC \>= 500/mm\^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

You may not qualify if:

• Concurrent enrollment in another therapeutic investigational study
• Prior treatment with venetoclax (or other investigational small molecule BCL2 inhibitors) or with copanlisib
• Prior allogeneic stem cell transplant
• Prior therapeutic intervention with any of the following:
• Therapeutic anticancer antibodies within 2 weeks
• Radio- or toxin-immunoconjugates within 10 weeks
• All other chemotherapy, radiation therapy within 30 days prior to initiation of therapy
• Targeted therapy within 6 half-lives
• Vaccinated with live vaccines within 4 weeks of the first dose of study drug
• Systemic continuous corticosteroid therapy at a daily dose higher than 20 mg prednisone or equivalent is not allowed. Participants may be using topical or inhaled corticosteroids
• Concurrent administration of medications or food that are strong inhibitors or inducers of CYP3A4 taken within 7 days of starting study treatment
• Current evidence of central nervous system involvement by the lymphoma
• Uncontrolled active systemic infection
• Unresolved toxicities (except alopecia) from prior anticancer therapy (including radiation) that have not resolved to grade =\< 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), or to the levels dictated in this protocol
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

copanlisib; venetoclax

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

Study Officials

• Alexey Danilov

  City of Hope Medical Cneter

  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: May 18, 2021
• First Posted: June 25, 2021
• Study Start: June 29, 2022
• Primary Completion (Estimated): February 12, 2027
• Study Completion (Estimated): February 12, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)