Trial Condition(s):

Lymphoma, Non-Hodgkin

Open-label, uncontrolled Phase II trial of intravenous PI3K inhibitor BAY80-6946 in patients with relapsed, indolent or aggressive Non-Hodgkin's lymphomas

Bayer Identifier:

16349

ClinicalTrials.gov Identifier:

NCT01660451

EudraCT Number:

2012-002602-52

Recruitment Complete

Trial Purpose

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 (CHRONOS-1) 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 4 years after last patient completed treatment. Patients who discontinue study drug for reasons other than disease progression will enter the Active Assessment Follow-up 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.

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)].

Trial Summary

Enrollment Goal
227
Trial Dates
black-arrow
Phase
2
Could I receive a placebo?
No
Products
Aliqopa (Copanlisib, BAY80-6946)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Investigative Site

Bologna, Italy, 40138

Status
Completed
 
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Investigative Site

Torino, Italy, 10126

Status
Completed
 
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Investigative Site

Roma, Italy, 00161

Status
Completed
 
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Napoli, Italy, 80131

Status
Completed
 
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Investigative Site

Manchester, United Kingdom, M20 4BX

Status
Completed
 
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Investigative Site

LILLE, France, 59037

Status
Completed
 
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Investigative Site

Pierre Benite, France, 69495

Status
Completed
 
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Investigative Site

Creteil, France, 94010

Status
Completed
 
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Investigative Site

Majadahonda, Spain, 28222

Status
Active, not recruiting
 
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Barcelona, Spain, 08036

Status
Completed
 
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Valencia, Spain, 46026

Status
Completed
 
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Sevilla, Spain, 41009

Status
Completed
 
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Marbella, Spain, 29603

Status
Completed
 
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Anderlecht, Belgium, 1070

Status
Completed
 
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GENT, Belgium, 9000

Status
Completed
 
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Investigative Site

BRUXELLES - BRUSSEL, Belgium, 1200

Status
Completed
 
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Investigative Site

LEUVEN, Belgium, 3000

Status
Completed
 
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San Antonio, United States, 78229

Status
Completed
 
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Sutton, United Kingdom, SM2 5PT

Status
Completed
 
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Leeds, United Kingdom, LS9 7TF

Status
Completed
 
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Investigative Site

PESSAC, France, 33600

Status
Active, not recruiting
 
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München, Germany, 81377

Status
Completed
 
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Berlin, Germany, 13353

Status
Completed
 
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Mainz, Germany, 55131

Status
Completed
 
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Southampton, United Kingdom, SO16 6YD

Status
Completed
 
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Liverpool, United Kingdom, L7 8XP

Status
Completed
 
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Plymouth, United Kingdom, PL6 8DH

Status
Completed
 
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PARIS cedex, France, 75475

Status
Completed
 
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Investigative Site

Helsinki, Finland, 00290

Status
Active, not recruiting
 
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Turku, Finland, FIN-20521

Status
Active, not recruiting
 
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Rouen, France, 76038

Status
Completed
 
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Saint John, Canada, E2L 4L2

Status
Completed
 
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Montreal, Canada, H3T 1E2

Status
Completed
 
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Investigative Site

St. Louis Park, United States, 55426

Status
Completed
 
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Investigative Site

Oulu, Finland, 90020

Status
Active, not recruiting
 
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Recklinghausen, Germany, 45659

Status
Completed
 
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Dresden, Germany, 01307

Status
Completed
 
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Cambridge, United Kingdom, CB2 0QQ

Status
Completed
 
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Investigative Site

Milano, Italy, 20089

Status
Active, not recruiting
 
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Uddevalla, Sweden, 451 80

Status
Completed
 
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Investigative Site

Brescia, Italy, 25123

Status
Completed
 
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Investigative Site

Detroit, United States, 48202

Status
Active, not recruiting
 
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Montreal, Canada, H1T 2M4

Status
Active, not recruiting
 
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Investigative Site

Port St. Lucie, United States, 34952

Status
Completed
 
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Investigative Site

Aurora, United States, 80012

Status
Active, not recruiting
 
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Investigative Site

Birmingham, United States, 35213

Status
Completed
 
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Investigative Site

BREST, France, 29285

Status
Completed
 
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VANDOEUVRE-LES-NANCY, France, 54500

Status
Completed
 
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Madrid, Spain, 28050

Status
Completed
 
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WILRIJK, Belgium, 2610

Status
Completed
 
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Investigative Site

Potsdam, Germany, 14467

Status
Completed
 
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Investigative Site

Anaheim, United States, 90801

Status
Active, not recruiting
 
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Investigative Site

Ramat Gan, Israel, 5262000

Status
Active, not recruiting
 
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Investigative Site

Petach Tikva, Israel, 4941492

Status
Completed
 
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Investigative Site

Ankara, Turkey, 06100

Status
Active, not recruiting
 
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Investigative Site

Izmir, Turkey, 35100

Status
Active, not recruiting
 
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Investigative Site

Istanbul, Turkey, 34093

Status
Active, not recruiting
 
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Investigative Site

Garran, Australia, 2605

Status
Active, not recruiting
 
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Investigative Site

Birmingham, United Kingdom, B9 5SS

Status
Completed
 
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Investigative Site

Harrow, United Kingdom, HA1 3UJ

Status
Completed
 
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Investigative Site

Romford, United Kingdom, RM7 0AG

Status
Completed
 
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Investigative Site

Nizhny Novgorod, Russia, 603126

Status
Completed
 
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Investigative Site

Moscow, Russia, 129128

Status
Completed
 
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Investigative Site

St. Petersburg, Russia, 197101

Status
Active, not recruiting
 
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Investigative Site

Seoul, South Korea, 03080

Status
Active, not recruiting
 
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Investigative Site

Seoul, South Korea, 06351

Status
Active, not recruiting
 
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Investigative Site

Busan, South Korea, 49201

Status
Completed
 
Locations

Investigative Site

Goldsboro, United States, 27534

Status
Completed
 
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Investigative Site

Spokane, United States, 99208-1129

Status
Active, not recruiting
 
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Investigative Site

Englewood, United States, 80113

Status
Completed
 
Locations

Investigative Site

Gilbert, United States, 85234

Status
Active, not recruiting
 
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Investigative Site

Fort Collins, United States, 80528

Status
Completed
 
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Investigative Site

Christchurch, New Zealand

Status
Completed
 
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Investigative Site

Saratov, Russia, 410053

Status
Completed
 
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Investigative Site

Louisville, United States, 40207

Status
Active, not recruiting
 
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Investigative Site

TURNHOUT, Belgium, 2300

Status
Completed
 
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Investigative Site

Tampere, Finland, 33521

Status
Completed
 
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Investigative Site

Berlin, Germany, 10967

Status
Completed
 
Locations

Investigative Site

Lake Success, United States, 11042

Status
Active, not recruiting
 
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Investigative Site

Omsk, Russia, 644013

Status
Completed
 
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Investigative Site

Kemerovo, Russia, 650066

Status
Completed
 
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Investigative Site

Izmir, Turkey, 35340

Status
Completed
 
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Investigative Site

Linz, Austria, 4020

Status
Completed
 
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Investigative Site

Singapore, Singapore, 169608

Status
Completed
 
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Investigative Site

Singapore, Singapore, 169610

Status
Completed
 
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Investigative Site

Hong Kong, Hong Kong, China, NA

Status
Completed
 
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Investigative Site

Shatin, Hong Kong, China

Status
Completed
 
Locations

Investigative Site

Münster, Germany, 48149

Status
Completed
 
Locations

Investigative Site

Lisboa, Portugal, 1099-023

Status
Active, not recruiting
 
Locations

Investigative Site

Budapest, Hungary, 1083

Status
Active, not recruiting
 
Locations

Investigative Site

Zerifin, Israel, 7030000

Status
Completed
 
Locations

Investigative Site

Kaposvar, Hungary, 7400

Status
Active, not recruiting
 
Locations

Investigative Site

Budapest, Hungary, 1097

Status
Completed
 
Locations

Investigative Site

POITIERS, France, 86021

Status
Completed
 
Locations

Investigative Site

Sofia, Bulgaria, 1431

Status
Active, not recruiting
 
Locations

Investigative Site

LA ROCHE SUR YON, France, 85925

Status
Completed
 
Locations

Investigative Site

Canton, United States, 44718

Status
Completed
 
Locations

Investigative Site

Galway, Ireland, H91 YR71

Status
Completed
 
Locations

Investigative Site

Gdynia, Poland, 81-519

Status
Completed
 
Locations

Investigative Site

Krakow, Poland, 30-510

Status
Completed
 
Locations

Investigative Site

Athens, Greece, 11526

Status
Completed
 

Trial Design