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Mantle Cell Lymphoma (MCL)Phase 1/2NCT03877055

A Study of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

A Phase 1/2 study testing Copanlisib and Ibrutinib in people with Mantle Cell Lymphoma (MCL), run by Memorial Sloan Kettering Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to test the safety and any good and bad side effects of combining 2 study drugs, copanlisib and ibrutinib. This combination of drugs could shrink your Mantle Cell Lymphoma (MCL), but it could also cause side effects. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma (MCL)
What is being tested?
Copanlisib and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
6 sitesUnited States
Study dates
13 Mar 2019to 7 Oct 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patient is ≥ 18 years of age at the time of signing Informed Consent
  • Patient is able and willing to adhere to the study visit schedule and other protocol requirements
  • Patient has histologically confirmed diagnosis of R/R mantle cell lymphoma who has received at least 1 line of therapy
  • °Autologous stem cell transplant recipients must have adequate bone marrow recovery and transfusion independent
  • Patients may have been previously treated with BTK or PI3K inhibitors:
  • °If BTK/P13K inhibitors were part of their last treatment, patients must have had a best response of stable disease or better
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  • Patient has at least one measurable lesion (≥ 2 cm) according to RECIL criteria[37]
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Patient has adequate bone marrow and organ function by:
  • Absolute neutrophil count (ANC) ≥ 1 x 10^9/L , independent of growth factor support for 14 days unless there is bone marrow involvement. For patients with bone marrow involvement, ANC ≥ 500/uL independent of growth factor support for 14 days
  • Platelets ≥100 x 10^9/L, or ≥50 x 10^9/L if bone marrow involvement and independent of transfusion support for 14 days in either situation
  • Hemoglobin (Hgb) ≥ 9.0 g/dL (no RBC transfusion within past 14 days)
  • International Normalized Ratio (INR) ≤ 1.5
  • Serum Creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 25 mL/min as determined by the Cockcroft-Gault equation or a 24 hour urine collection
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN (or ≤ 3 x ULN if liver involved with disease
  • Total serum bilirubin ≤ ULN (or ≤ 1.5 x ULN if documented hepatic involvement; or total bilirubin ≤ 3 x ULN with direct bilirubin ≤ 1.5 x ULN in patients with documented Gilbert's Syndrome.
  • Lipase ≤ 1.5x ULN
  • LVEF ≥ 50%
  • Hemoglobin A1c ≤ 8.5%

Who cannot join

  • Patient has a history of non-compliance to medical regimen or inability to grant consent
  • Patient is concurrently using other approved or investigational antineoplastic agent with the exception of BTK or Pi3K inhibitors in patients who had these agents as the last line of treatment
  • °Patient on BTK or P13K inhibitors will be continued on therapy as they transition to protocol therapy
  • Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
  • Patient has had major surgery or a wound that has not fully healed within 4 weeks of starting study drugs.
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
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  • Patients who have undergone an allogenic hematopoietic stem cell transplant
  • Patient has active or history of central nervous system (CNS) disease or meningeal involvement.
  • Patient has history of clinically significant interstitial lung disease and/or lung disease that severely impairs lung function (as judged by the investigator)
  • Patient has history of stroke or intracranial hemorrhage ≤ 6 months from starting study drugs.
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Patient has clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO), unstable angina pectoris, symptomatic pericarditis, QTcF > 480 msec on the screening ECG (using the QTcF formula)
  • Patient has a concurrent active malignancy. Malignancies treated with a curative intent with an expected life expectancy ≥ 5 years or a non-competing life expectancy risk are eligible (i.e. adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, early stage breast cancer, treated prostate cancer or any other cancer from which the patient has been disease free for ≥ 3 years).
  • Patient with known history of human immunodeficiency virus (HIV), or any uncontrolled active systemic infection.
  • Patient has CMV viremia (peripheral blood CMV PCR positive), acute viral hepatitis (typically defined by elevated AST/ALT), or a history of chronic or active HBV or HCV infection. HBV infection is defined as having HBsAg and/or HBcAb positive test with concurrent detectable HBV DNA levels. HCV infection is defined as detectable HCV RNA levels.
  • Patient requires treatment with a strong or moderate cytochrome P450 (CYP) 3A4 inhibitors, and inducers, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Moderate and strong CYP modulators (inducers and inhibitors) should have a washout period of at least 5-6 half-lives before initiating ibrutinib or copanlisib.
  • Patients with known bleeding diathesis (e.g. von Willebrand 's disease) or hemophilia
  • Patient is currently receiving warfarin or other Vitamin K antagonist. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. Refer to Section 9.5 for Concomitant medication
  • Patients with Child Pugh Class B or C hepatic cirrhosis
  • Patients with any life threatening illness, medical condition or organ system dysfunction that in the opinion of the investigator could compromise the subject's safety, interfere with absorption of metabolism of study drugs or put the study outcomes at undue risk.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Phase I/II Clinical Trial of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

The purpose of this study is to test the safety and any good and bad side effects of combining 2 study drugs, copanlisib and ibrutinib. This combination of drugs could shrink your Mantle Cell Lymphoma (MCL), but it could also cause side effects. Both these drugs have been given to people before, but this is the first time that they are being given together.

Being tested
Copanlisib, Ibrutinib
Keywords
Copanlisib, Ibrutinib, 18-450
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.

  • CopanlisibDrug

    Treatment will be with intravenous copanlisib on days 1, 8, 15 of 28 day cycles.

  • IbrutinibDrug

    Oral ibrutinib daily in 28 day cycles. A cycle is defined as 28 days of therapy.

Study groups in NCT03877055
Study groupRoleWhat they receive
Copanlisib and IbrutinibExperimentalCopanlisib is given intravenously on days 1, 8, and 15 of 28 day cycles. Ibrutinib is given orally every day on 28 days cycles. The maximum duration of treatment is 36 cycles not exceeding 36 months. In the phase II study, the cohort will expand and accrue patients at the recommended phase II dose of copanlisib and ibrutinib determined during phase I dose escalation. In a simon two stage mini-max design, an initial 18 patients will be enrolled, inclusive of 6 patients treated at MTD or RP2D from phase I study, in first stage.
Receives: Drug: Copanlisib; Drug: Ibrutinib

What is being measured

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

  1. Complete Response

    using the RECIL criteria

    Measured: 2 years

Timeline

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

  1. First posted15 Mar 2019
  2. Study start13 Mar 2019
  3. Primary completion7 Oct 2022
  4. Study completion7 Oct 2022

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
Sequential
Model description
This is a two stage protocol comprised of a single institution phase I dose escalation trial using standard 3+3 design and a phase II two stage Simon mini-max clinical trial.
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03877055
Sponsor's protocol ID
18-450
Status last verified
Oct 2022
First submitted
14 Mar 2019
Last updated
14 Dec 2022
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Copanlisib and Ibrutinib in people with Mantle Cell Lymphoma (MCL), run by Memorial Sloan Kettering Cancer Center at 6 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 19 inclusion and 20 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: finished, as of the sponsor's last update on 14 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 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?

Yes. Results are posted in the registry (first posted 14 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Complete Response (time frame: 2 years). 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 NCT03877055.

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 14 Dec 2022.

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