Clinical Trials /

A Study of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

NCT03877055

Description:

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.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Copanlisib and Ibrutinib in Mantle Cell Lymphoma
  • Official Title: Phase I/II Clinical Trial of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 18-450
  • NCT ID: NCT03877055

Conditions

  • Mantle Cell Lymphoma (MCL)

Interventions

DrugSynonymsArms
CopanlisibCopanlisib and Ibrutinib
IbrutinibCopanlisib and Ibrutinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Copanlisib
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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%

        Exclusion Criteria:

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response (Phase II)
Time Frame:2 years
Safety Issue:
Description:using the RECIL criteria

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Copanlisib
  • Ibrutinib
  • 18-450

Last Updated

October 24, 2019