Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Conditions
Lymphoma, Non-Hodgkin
Conditions: official terms
Lymphoma - Lymphoma, Non-Hodgkin
Conditions: Keywords
Clinical trial, phase II, Phosphatidylinositol 3-Kinase, Class I, Non-Hodgkin's lymphoma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Copanlisib (BAY80-6946)
Type: Drug
Overall Status
Recruiting
Summary
The objective of the study (part A) is to evaluate the efficacy and safety of BAY80-6946 in patients with indolent or aggressive Non-Hodgkin's Lymphoma, who have progressed after standard therapy. 30 patients will be enrolled to both indolent and aggressive disease group. The objective of the study part B is to evaluate the efficacy and safety of BAY80-6946 in patients with relapsed/refractory follicular lymphoma. 120 patients will be enrolled in the part B of the study. Further objectives are to evaluate the pharmacokinetics and biomarkers. Quality of life will be a further objective of part B of the study.

In a cohort of 20 patients (enrolled both in part A and B) an ECG substudy will be performed to assess the potential for cardiac toxicity and QT/QTc interval prolongation of BAY80-6946.

After an up to 28-day screening period, eligible patients will start treatment with BAY80-6946 at a dose of 0.8 mg/kg (Part A) and at a dose of 60 mg (Part B).

Treatment will be continued until disease has progressed or until another criterion is met for withdrawal from study. An end-of-treatment visit will be performed within 7 days after discontinuation of study treatment. Thirty to 35 days after last study drug administration, a safety followup visit will be performed for the collection of adverse events (AEs) and concomitant medication data. Patients will be contacted quarterly to determine overall survival status up to 3 years after last patient first treatment. In Part B, patients will enter the Active Assessment Followup Period. The end of study notification to Health Authorities will be based on the completion of the collection of survival data.

The efficacy is measured by the decrease in tumor size. Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. Blood samples will be collected for pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis (mandatory) and for central pathology review (part B), fresh biopsy tissue will also be collected if available.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Indolent NHL:

- Histologically confirmed diagnosis of follicular lymphoma (FL) grades 1, 2 or 3a, marginal zone lymphoma (including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue [MALT] lymphoma), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, chronic lymphocytic leukemia (CLL).

- Relapsed after ≥ 2 prior chemotherapy- or immunotherapy-based regimens for indolent NHL, or refractory to 2 prior chemotherapy and/ or immunotherapy-based regimens.

- Aggressive NHL:

- Histologically confirmed diagnosis of grade 3b follicular lymphoma (FL), transformed indolent lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal large B-cell lymphoma, mantle cell lymphoma (MCL), peripheral T-cell lymphoma unspecified, or anaplastic large cell lymphoma primary systemic type, or angioimmunoblastic T cell lymphoma.

- Relapsed after ≥ 2 prior chemotherapy regimens, including the following: First-line treatment with standard anthracycline-containing regimen (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone or equivalent). At least 1 additional combination chemotherapy regimen. Patients relapsed after or refractory to first prior chemotherapy- and/or immunotherapy-based regimen for aggressive NHL and not eligible for high-dose regimen followed by transplant. High-dose chemotherapy, or chemoradiotherapy with autologous stem cell transplantation is considered 1 regimen. Patients with CD20 expressing neoplastic cells must have received prior rituximab, if available.

- Patients with transformed indolent lymphoma must have received at least 2 prior chemotherapy- and/or immunotherapy-based regimens

- Consent to provide fresh tumor tissue during screening

- Indolent B-cell NHL lymphoma (study part B):

- Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:

- Follicular lymphoma (FL) grade 1-2-3a

- Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry

- Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)

- Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)

- Relapsed or refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received Rituximab and alkylating agents.

- For all patients:

- Male or female patients > 18 years of age

- ECOG performance status ≤ 2 (ECOG: Eastern Cooperative Oncology Group)

- Life expectancy of at least 3 months

- Adequate bone marrow, liver and renal function as assessed within 7 days before starting study treatment

- Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) for the Institution

- Availability of archival tumor tissue

Exclusion Criteria:

- Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg despite optimal medical management)

- Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks of start of study medication (CTCAE: Common Terminology Criteria for Adverse Events).

- History or concurrent condition of interstitial lung disease

- Unresolved toxicity higher than CTCAE grade 1 (NCI-CTC version 4.0) attributed to any prior therapy/procedure excluding alopecia. (NCI: National Cancer Institute)

- Prior treatment with PI3K inhibitors

- Systemic corticosteroid therapy (ongoing)

- Hepatitis B or C. All subjects must be screened for hepatitis B and C up to 28 days prior to study drug start using the hepatitis virus panel laboratorial routine. Subjects positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; subjects positive for HCV IgG will be eligible if they are negative for HCV RNA.

- For Part B:

- Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease and chronic lymphocytic leukemia (CLL)

- History or concurrent condition of interstitial lung disease or severely impaired pulmonary function

- Excluded medical conditions:

- Previous or concurrent cancer that is distinct in primary site or histology from indolent B-cell NHL within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].

- Hepatitis B or C. All subjects must be screened for hepatitis B and C up to 28 days prior to study drug start using the hepatitis virus panel laboratorial routine. Subjects positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; subjects positive for HCV IgG will be eligible if they are negative for HCV-RNA.

- Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma glucose > 160 mg/dL at screening.

- Previous or concurrent cancer that is distinct in primary site or histology from indolent B-cell NHL within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
Locations
Birmingham, Alabama, United States
Status: Recruiting
Anchorage, Alaska, United States
Status: Not yet recruiting
Gilbert, Arizona, United States
Status: Terminated
Anaheim, California, United States
Status: Recruiting
Encinitas, California, United States
Status: Not yet recruiting
Fresno, California, United States
Status: Not yet recruiting
Los Angeles, California, United States
Status: Terminated
Los Angeles, California, United States
Status: Terminated
Pleasant Hill, California, United States
Status: Terminated
San Diego, California, United States
Status: Recruiting
Aurora, Colorado, United States
Status: Recruiting
Englewood, Colorado, United States
Status: Recruiting
Fort Collins, Colorado, United States
Status: Recruiting
Boca Raton, Florida, United States
Status: Terminated
Miami Gardens, Florida, United States
Status: Terminated
Orlando, Florida, United States
Status: Terminated
Port St. Lucie, Florida, United States
Status: Recruiting
Athens, Georgia, United States
Status: Recruiting
Joliet, Illinois, United States
Status: Terminated
Evansville, Indiana, United States
Status: Terminated
Sioux City, Iowa, United States
Status: Recruiting
Westwood, Kansas, United States
Status: Terminated
Louisville, Kentucky, United States
Status: Recruiting
Alexandria, Louisiana, United States
Status: Recruiting
Metairie, Louisiana, United States
Status: Terminated
Brewer, Maine, United States
Status: Terminated
Bethesda, Maryland, United States
Status: Terminated
Boston, Massachusetts, United States
Status: Recruiting
Boston, Massachusetts, United States
Status: Recruiting
Detroit, Michigan, United States
Status: Recruiting
Lansing, Michigan, United States
Status: Recruiting
Southfield, Michigan, United States
Status: Terminated
St. Louis Park, Minnesota, United States
Status: Recruiting
Columbia, Missouri, United States
Status: Terminated
Springfield, Missouri, United States
Status: Recruiting
Billings, Montana, United States
Status: Recruiting
Egg Harbor Township, New Jersey, United States
Status: Terminated
Morristown, New Jersey, United States
Status: Terminated
New Brunswick, New Jersey, United States
Status: Recruiting
Lake Success, New York, United States
Status: Terminated
Lake Success, New York, United States
Status: Recruiting
Goldsboro, North Carolina, United States
Status: Recruiting
Canton, Ohio, United States
Status: Not yet recruiting
Cleveland, Ohio, United States
Status: Terminated
Tulsa, Oklahoma, United States
Status: Not yet recruiting
Pittsburgh, Pennsylvania, United States
Status: Terminated
Charleston, South Carolina, United States
Status: Not yet recruiting
Charleston, South Carolina, United States
Status: Terminated
Greenville, South Carolina, United States
Status: Recruiting
Nashville, Tennessee, United States
Status: Recruiting
San Antonio, Texas, United States
Status: Recruiting
Salt Lake City, Utah, United States
Status: Not yet recruiting
Spokane, Washington, United States
Status: Recruiting
Green Bay, Wisconsin, United States
Status: Recruiting
Garran, Australian Capital Territory, Australia
Status: Recruiting
Innsbruck, Tirol, Austria
Status: Terminated
Graz, Austria
Status: Not yet recruiting
Linz, Austria
Status: Not yet recruiting
Antwerpen, Belgium
Status: Terminated
Brugge, Belgium
Status: Terminated
Bruxelles - Brussel, Belgium
Status: Recruiting
Bruxelles - Brussel, Belgium
Status: Recruiting
Charleroi, Belgium
Status: Not yet recruiting
Edegem, Belgium
Status: Not yet recruiting
Gent, Belgium
Status: Completed
Leuven, Belgium
Status: Recruiting
Ottignies, Belgium
Status: Not yet recruiting
Turnhout, Belgium
Status: Not yet recruiting
Wilrijk, Belgium
Status: Recruiting
Saint John, New Brunswick, Canada
Status: Recruiting
Montreal, Quebec, Canada
Status: Recruiting
Montreal, Quebec, Canada
Status: Recruiting
Beijing, Guangdong, China
Status: Suspended
Guangzhou, Guangdong, China
Status: Suspended
Shanghai, Guangdong, China
Status: Suspended
Beijing, China
Status: Suspended
Montería, Córdoba, Colombia
Status: Not yet recruiting
Bucaramanga, Santander, Colombia
Status: Not yet recruiting
Cali, Valle del Cauca, Colombia
Status: Not yet recruiting
Medellín, Colombia
Status: Not yet recruiting
Aalborg, Denmark
Status: Not yet recruiting
AarhusC, Denmark
Status: Not yet recruiting
Copenhagen, Denmark
Status: Not yet recruiting
Odense C, Denmark
Status: Not yet recruiting
HUS, Finland
Status: Recruiting
Jyväskylä, Finland
Status: Not yet recruiting
Oulu, Finland
Status: Not yet recruiting
Tampere, Finland
Status: Recruiting
Turku, Finland
Status: Recruiting
Angers Cedex 01, France
Status: Not yet recruiting
Bayonne, France
Status: Not yet recruiting
Brest, France
Status: Not yet recruiting
Clermont- Ferrand, France
Status: Not yet recruiting
Creteil, France
Status: Recruiting
La Roche Sur Yon, France
Status: Not yet recruiting
Lille, France
Status: Recruiting
Limoges, France
Status: Not yet recruiting
NICE Cedex 2, France
Status: Not yet recruiting
PARIS cedex, France
Status: Recruiting
Pessac, France
Status: Recruiting
Pierre Benite, France
Status: Recruiting
Poitiers, France
Status: Not yet recruiting
Rouen, France
Status: Recruiting
Saint-denis Cedex, France
Status: Not yet recruiting
Tours, France
Status: Not yet recruiting
Vandoeuvre-les-nancy, France
Status: Recruiting
Augsburg, Bayern, Germany
Status: Not yet recruiting
München, Bayern, Germany
Status: Recruiting
Potsdam, Berlin, Germany
Status: Recruiting
Münster, Nordrhein-Westfalen, Germany
Status: Recruiting
Recklinghausen, Nordrhein-Westfalen, Germany
Status: Recruiting
Mainz, Rheinland-Pfalz, Germany
Status: Recruiting
Homburg, Saarland, Germany
Status: Not yet recruiting
Dresden, Sachsen, Germany
Status: Not yet recruiting
Berlin, Germany
Status: Not yet recruiting
Berlin, Germany
Status: Recruiting
Athens, Attica, Greece
Status: Not yet recruiting
Haidari, Attica, Greece
Status: Not yet recruiting
Athens, Greece
Status: Not yet recruiting
Thessaloniki, Greece
Status: Not yet recruiting
Shatin, New Territories, Hong Kong
Status: Not yet recruiting
Hong Kong, Hong Kong
Status: Not yet recruiting
Budapest, Hungary
Status: Not yet recruiting
Budapest, Hungary
Status: Not yet recruiting
Kaposvar, Hungary
Status: Not yet recruiting
Dublin, Ireland
Status: Not yet recruiting
Dublin, Ireland
Status: Not yet recruiting
Galway, Ireland
Status: Not yet recruiting
Beer Sheva, Israel
Status: Terminated
Kfar Saba, Israel
Status: Not yet recruiting
Petach Tikva, Israel
Status: Recruiting
Tel Aviv, Israel
Status: Terminated
Tel Hashomer, Israel
Status: Recruiting
Zerifin, Israel
Status: Not yet recruiting
Rozzano, Milano, Italy
Status: Recruiting
Bologna, Italy
Status: Recruiting
Brescia, Italy
Status: Recruiting
Napoli, Italy
Status: Recruiting
Roma, Italy
Status: Recruiting
Torino, Italy
Status: Recruiting
Nagoya, Aichi, Japan
Status: Terminated
Nagoya, Aichi, Japan
Status: Terminated
Nagoya, Aichi, Japan
Status: Terminated
Kashiwa, Chiba, Japan
Status: Terminated
Isehara, Kanagawa, Japan
Status: Terminated
Chuo-ku, Tokyo, Japan
Status: Terminated
Koto-ku, Tokyo, Japan
Status: Terminated
Fukuoka, Japan
Status: Terminated
Busan, Busan Gwang''yeogsi, Korea, Republic of
Status: Recruiting
Seoul, Seoul Teugbyeolsi, Korea, Republic of
Status: Recruiting
Seoul, Korea, Republic of
Status: Recruiting
Esch-sur-Alzette, Luxembourg
Status: Not yet recruiting
Luxembourg, Luxembourg
Status: Not yet recruiting
Christchurch, New Zealand
Status: Recruiting
Gdynia, Poland
Status: Not yet recruiting
Krakow, Poland
Status: Not yet recruiting
Lublin, Poland
Status: Not yet recruiting
Warszawa, Poland
Status: Not yet recruiting
Wroclaw, Poland
Status: Not yet recruiting
Lisboa, Portugal
Status: Not yet recruiting
Kemerovo, Russian Federation
Status: Recruiting
Moscow, Russian Federation
Status: Not yet recruiting
Moscow, Russian Federation
Status: Terminated
Nizhny Novgorod, Russian Federation
Status: Recruiting
Omsk, Russian Federation
Status: Recruiting
Samara, Russian Federation
Status: Not yet recruiting
Saratov, Russian Federation
Status: Recruiting
St. Petersburg, Russian Federation
Status: Not yet recruiting
St. Petersburg, Russian Federation
Status: Terminated
St. Petersburg, Russian Federation
Status: Recruiting
Singapore, Singapore
Status: Not yet recruiting
Singapore, Singapore
Status: Not yet recruiting
Majadahonda, Madrid, Spain
Status: Recruiting
Marbella, Málaga, Spain
Status: Recruiting
Barcelona, Spain
Status: Completed
Madrid, Spain
Status: Recruiting
Sevilla, Spain
Status: Recruiting
Valencia, Spain
Status: Recruiting
Falun, Sweden
Status: Not yet recruiting
Uddevalla, Sweden
Status: Recruiting
Ankara, Turkey
Status: Not yet recruiting
Ankara, Turkey
Status: Active, not recruiting
Istanbul, Turkey
Status: Active, not recruiting
Izmir, Turkey
Status: Active, not recruiting
Izmir, Turkey
Status: Not yet recruiting
Cambridge, Cambridgeshire, United Kingdom
Status: Recruiting
Plymouth, Devon, United Kingdom
Status: Recruiting
Southampton, Hampshire, United Kingdom
Status: Recruiting
Harrow, London, United Kingdom
Status: Recruiting
Liverpool, Merseyside, United Kingdom
Status: Completed
Sutton, Surrey, United Kingdom
Status: Recruiting
Birmingham, West Midlands, United Kingdom
Status: Recruiting
Leeds, United Kingdom
Status: Completed
Manchester, United Kingdom
Status: Recruiting
Romford, United Kingdom
Status: Recruiting
Start Date
November 2012
Completion Date
July 2018
Sponsors
Bayer
Source
Bayer
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page