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Recurrent Mantle Cell LymphomaPhase 1/2NCT04939272

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

A Phase 1/2 study testing Copanlisib Hydrochloride and Venetoclax in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Copanlisib Hydrochloride and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
29 Jun 2022to 12 Feb 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Platelets >= 50,000/mm^3 without bone marrow involvement or platelets >= 30,000/mm^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease or documented liver/biliary involvement by the lymphoma) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Left ventricular ejection fraction (LVEF) >= 45% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Lipase =< 1.5 ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Glycosylated hemoglobin (HbA1c) =< 8.5% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 30 days after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) without an alternative medical cause.

Who cannot join

  • 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
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  • 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
  • Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded
  • 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., breast, cervical, esophageal, etc.) without evidence of disease
  • Asymptomatic prostate cancer managed with "watch and wait" strategy or hormonal therapy
  • Major surgery within 4 weeks of the first dose of study drug
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening
  • Uncontrolled arterial hypertension despite optimal medical management
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function, such as patients requiring oxygen supplementation
  • Uncontrolled diabetes mellitus despite optimal medical management (per investigator's opinion)
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 3 months before the start of study medication
  • Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Copanlisib and Venetoclax in Patients With Relapsed or Refractory Mantle Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety, tolerability, and the maximum tolerated dose (MTD) of copanlisib hydrochloride (copanlisib) and venetoclax in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Phase 1) II. To estimate the efficacy (as measured by overall rate of response [ORR]) of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2)

SECONDARY OBJECTIVES:

  1. To characterize the safety profile of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) II. To evaluate duration of response (DOR) and progression-free survival (PFS) associated with combined administration of copanlisib/venetoclax. (Phase 2) III. To evaluate an overall survival (OS) associated with combined administration of copanlisib/venetoclax. (Phase 2) IV. To characterize the pharmacokinetics (PK) profile of copanlisib and venetoclax. (Phase 2)

EXPLORATORY OBJECTIVES:

  1. Evaluate the emergence of resistant clones, as determined by the presence of novel mutations and expression of BCL2 family proteins.

II. Characterize the T-cell population balance in patients treated with copanlisib/venetoclax.

OUTLINE: This is a phase I, dose-escalation study of copanlisib hydrochloride, followed by a phase II study.

Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15, and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Being tested
Copanlisib Hydrochloride, Venetoclax
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Copanlisib HydrochlorideDrug

    Also called 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

    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.

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    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.

Study groups in NCT04939272
Study groupRoleWhat they receive
Treatment (copanlisib hydrochloride, venetoclax)ExperimentalPatients 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.
Receives: Drug: Copanlisib Hydrochloride; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (6)

  1. Duration of response

    Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.

    Measured: 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

  2. Progression-free survival

    Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.

    Measured: 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

  3. Overall survival

    Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.

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

  4. Incidence of adverse events

    Toxicity and adverse events will be recorded using the NCI CTCAE 5.0 scale. Safety and tolerability of copanlisib in conjunction with venetoclax will be summarized for all patients (evaluable for toxicity) combined and by dose level (if patients were treated at both dose level [DL]1 and DL-1). Adverse events will be tabulated and summarized by major organ category, grade, and drug attribution. Severe adverse event specific incidence and exact 95% confidence interval will be provided where necessary/appropriate.

    Measured: Up to 90 days after completion of treatment

  5. Plasma pharmacokinetics (PK) of copanlisib (Cmax)

    Maximum plasma concentration (Cmax).

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

  6. Plasma pharmacokinetics (PK) of copanlisib (AUC)

    Area under the Curve (AUC).

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2021
  2. Study start29 Jun 2022
  3. Primary completion12 Feb 2027 (estimated)
  4. Study completion12 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04939272
Sponsor's protocol ID
22043
Other IDs
NCI-2021-03219, 22043, P30CA033572
Status last verified
Apr 2026
First submitted
18 May 2021
Last updated
20 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Copanlisib Hydrochloride and Venetoclax in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (Phase I) (time frame: Up to end of cycle 2 (1 cycle = 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04939272.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.

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