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Chronic Lymphocytic LeukemiaPhase 1NCT03884998

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

A Phase 1 study testing Copanlisib and Nivolumab in people with Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 3 sites 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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Copanlisib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
3 sitesUnited States
Study dates
10 Jul 2019to 7 Oct 2027
Phase
Phase 1
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

  • 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).
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  • 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
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy) must:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 1 month after the last dose of copanlisib, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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.
  • A history of human immunodeficiency virus (HIV) infection. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with copanlisib and/or nivolumab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Major surgery (under general anesthesia) within 30 days prior to therapy.
  • Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV), or history of HCV.
  • Live vaccine within 30 days.
  • Prior PD1, PD-L 1 or checkpoint inhibitors including CTLA4, Lag3, 41BB etc. within 2 years, or at any time if administered with the intent to treat Richter syndrome.
  • Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment, well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible.
  • Evidence of central nervous system (CNS) involvement.
  • Use of strong CYP3A4 inhibitors or inducers within 2 weeks prior to starting study therapy.
  • History or concurrent condition of interstitial lung disease and/or severely impaired lung function.
  • Patients with hemoglobin (Hb) A1c > 8.5% at screening.
  • Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment).
  • Patients with uncontrolled coagulopathy or bleeding disorder.
  • The following cardiovascular abnormalities:
  • Congestive heart failure >= class 3 New York Heart Association (NYHA) class.
  • Unstable angina (angina symptoms at rest), new-onset angina (onset within the last 3 months).
  • Myocardial infarction less than 6 months before start of study treatment.
  • Left ventricular ejection fraction (LVEF) less than 45%.
  • Corrected QT interval (QTc) > 480 msec (if echocardiogram performed during screening).
  • Females who are pregnant or nursing. Pregnant individuals are excluded from this study because copanlisib and nivolumab have the potential to cause fetal harm based on relevant animal studies (Refer to the appropriate prescribing information). Because there is an unknown but potential risk for adverse events in nursing infants, breast-/chest-feeding should be discontinued prior to treatment with copanlisib and nivolumab.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope Medical Center

    Duarte, California, 91010

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase I Study of PI3Kα,δ Inhibitor Copanlisib in Combination With PD-1 Antagonist Nivolumab in Patients With Transformed Chronic Lymphocytic Leukemia (Richter's Transformation) or Non-Hodgkin Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the maximum-tolerated dose (MTD) of copanlisib administered in combination with nivolumab in patients with transformed chronic lymphocytic leukemia (CLL)/non-Hodgkin's lymphoma (NHL).

SECONDARY OBJECTIVE:

  1. To evaluate the preliminary efficacy of copanlisib administered in combination with nivolumab in patients with transformed CLL/NHL.

EXPLORATORY OBJECTIVES:

  1. To evaluate the T-cell repertoire and activation patterns following dual targeting of PI3K and PD-1.

II. To establish if PD-1/PD-L 1 expression correlates with response to the combination of copanlisib and nivolumab.

OUTLINE: This is a dose-escalation study of copanlisib.

Patients receive copanlisib intravenously (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 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Being tested
Copanlisib, Nivolumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • CopanlisibDrug

    Also called BAY 80-6946, PI3K Inhibitor BAY 80-6946

    Given IV

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

Study groups in NCT03884998
Study groupRoleWhat they receive
Treatment (copanlisib and nivolumab)ExperimentalPatients 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.
Receives: Drug: Copanlisib; Biological: Nivolumab

What is being measured

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

  1. 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.

    Measured: Up to day 28

  2. 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.

    Measured: Up to 48 weeks

Secondary outcomes (3)

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

    Will be summarized with 95% confidence intervals.

    Measured: Up to 48 weeks

  2. Duration of response

    Will be summarized descriptively using means and standard deviation along with 95% confidence interval.

    Measured: Up to 48 weeks

  3. Progression-free survival (PFS)

    Will be summarized descriptively using the Kaplan-Meier estimate along with 95% confidence interval. We will also perform subset analysis with subjects who were treated at the maximum tolerated dose (MTD).

    Measured: Up to 48 weeks

Timeline

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

  1. First posted21 Mar 2019
  2. Study start10 Jul 2019
  3. Primary completion7 Oct 2027 (estimated)
  4. Study completion7 Oct 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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03884998
Sponsor's protocol ID
20066
Other IDs
NCI-2018-01880, STUDY00018655, 20066, P30CA033572
Status last verified
Oct 2026
First submitted
19 Mar 2019
Last updated
29 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Copanlisib and Nivolumab in people with Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 3 sites 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 20 inclusion and 34 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 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 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.

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 of copanlisib in combination with nivolumab (time frame: Up to day 28). 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 NCT03884998.

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 29 Oct 2026.

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