A Study of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

NCT03877055 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 18-450
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 6

Brief 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. Both these drugs have been given to people before, but this is the first time that they are being given together.

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

Copanlisib; Ibrutinib; 18-450

Outcome Measures

Primary Outcomes (1)

• Complete Response

  using the RECIL criteria

  2 years

Study Arms (1)

Copanlisib and Ibrutinib

EXPERIMENTAL

Copanlisib 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.

Drug: Copanlisib; Drug: Ibrutinib

Interventions

Copanlisib DRUG

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

Copanlisib and Ibrutinib

Ibrutinib DRUG

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

Copanlisib and Ibrutinib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator

Study Sites (6)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

copanlisib; ibrutinib

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

Results Point of Contact

• Title: Dr. Gilles Salles, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

SallesG@mskcc.org

646-608-4153

Study Officials

• Connie Batlevi, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 15, 2019
• Study Start: March 13, 2019
• Primary Completion: October 7, 2022
• Study Completion: October 7, 2022
• Last Updated: December 14, 2022
• Results First Posted: December 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (6)