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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01660451




Registration number
NCT01660451
Ethics application status
Date submitted
6/08/2012
Date registered
8/08/2012

Titles & IDs
Public title
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Scientific title
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Secondary ID [1] 0 0
2012-002602-52
Secondary ID [2] 0 0
16349
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Copanlisib (Aliqopa, BAY80-6946)

Experimental: Copanlisib (indolent NHL) - Part A: Participants in this arm will be patients with indolent NHL.

Experimental: Copanlisib (aggressive NHL) - Part A: Participants in this arm will be patients with aggressive NHL.

Experimental: Copanlisib (indolent B-cell NHL) - Part B: Participants in this arm will be patients with indolent B-cell NHL.


Treatment: Drugs: Copanlisib (Aliqopa, BAY80-6946)
BAY 80-6946 is administered in a normal saline solution, 100 mL, intravenously over 1h. No intravenous glucose preparations should be administered on the days of infusion. Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).

Part A: The individual dose will be 0.8 mg/kg (max. 65 mg) per infusion from Cycle 1 on. The maximum dose of 65 mg should never be exceeded.

Part B: The individual dose will be 60 mg per infusion from Cycle 1 on.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) Based on Independent Review-Part A
Timepoint [1] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [2] 0 0
ORR Based on Independent Review-Part B
Timepoint [2] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [3] 0 0
ORR Based on Investigator Assessment-Part A
Timepoint [3] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [4] 0 0
ORR Based on Investigator Assessment-Part B
Timepoint [4] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [1] 0 0
Duration of Response (DOR) Based on Independent Review-Part A
Timepoint [1] 0 0
Baseline up to approximately 6 years
Secondary outcome [2] 0 0
DOR Based on Independent Review-Part B
Timepoint [2] 0 0
Baseline up to approximately 9 years 7 months
Secondary outcome [3] 0 0
DOR Based on Investigator Assessment-Part A
Timepoint [3] 0 0
Baseline up to approximately 6 years
Secondary outcome [4] 0 0
DOR Based on Investigator Assessment-Part B
Timepoint [4] 0 0
Baseline up to approximately 9 years 7 months
Secondary outcome [5] 0 0
Progression Free Survival (PFS) Based on Independent Review-Part A
Timepoint [5] 0 0
Baseline up to approximately 6 years
Secondary outcome [6] 0 0
PFS Based on Independent Review-Part B
Timepoint [6] 0 0
Baseline up to approximately 9 years 7 months
Secondary outcome [7] 0 0
PFS Based on Investigator Assessment-Part A
Timepoint [7] 0 0
Baseline up to approximately 6 years
Secondary outcome [8] 0 0
PFS Based on Investigator Assessment-Part B
Timepoint [8] 0 0
Baseline up to approximately 9 years 7 months
Secondary outcome [9] 0 0
Overall Survival (OS)-Part A
Timepoint [9] 0 0
Baseline up to approximately 6 years
Secondary outcome [10] 0 0
OS-Part B
Timepoint [10] 0 0
Baseline up to approximately 9 years 7 months
Secondary outcome [11] 0 0
Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B
Timepoint [11] 0 0
Baseline up to week 16
Secondary outcome [12] 0 0
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B
Timepoint [12] 0 0
Baseline up to week 16

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)].

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT
Recruitment hospital [1] 0 0
- Garran
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Austria
State/province [14] 0 0
Linz
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles - Brussel
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Belgium
State/province [17] 0 0
Gent
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Turnhout
Country [20] 0 0
Belgium
State/province [20] 0 0
Wilrijk
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Sofia
Country [22] 0 0
Canada
State/province [22] 0 0
New Brunswick
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Finland
State/province [24] 0 0
Helsinki
Country [25] 0 0
Finland
State/province [25] 0 0
Oulu
Country [26] 0 0
Finland
State/province [26] 0 0
Tampere
Country [27] 0 0
Finland
State/province [27] 0 0
Turku
Country [28] 0 0
France
State/province [28] 0 0
Brest
Country [29] 0 0
France
State/province [29] 0 0
Creteil
Country [30] 0 0
France
State/province [30] 0 0
La Roche Sur Yon
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
PARIS cedex
Country [33] 0 0
France
State/province [33] 0 0
Pessac
Country [34] 0 0
France
State/province [34] 0 0
Pierre Benite
Country [35] 0 0
France
State/province [35] 0 0
Poitiers
Country [36] 0 0
France
State/province [36] 0 0
Rouen
Country [37] 0 0
France
State/province [37] 0 0
Vandoeuvre-les-nancy
Country [38] 0 0
Germany
State/province [38] 0 0
Bayern
Country [39] 0 0
Germany
State/province [39] 0 0
Berlin
Country [40] 0 0
Germany
State/province [40] 0 0
Nordrhein-Westfalen
Country [41] 0 0
Germany
State/province [41] 0 0
Rheinland-Pfalz
Country [42] 0 0
Germany
State/province [42] 0 0
Sachsen
Country [43] 0 0
Greece
State/province [43] 0 0
Athens
Country [44] 0 0
Hong Kong
State/province [44] 0 0
Hong Kong
Country [45] 0 0
Hong Kong
State/province [45] 0 0
Shatin
Country [46] 0 0
Hungary
State/province [46] 0 0
Budapest
Country [47] 0 0
Hungary
State/province [47] 0 0
Kaposvar
Country [48] 0 0
Ireland
State/province [48] 0 0
Galway
Country [49] 0 0
Israel
State/province [49] 0 0
Petach Tikva
Country [50] 0 0
Israel
State/province [50] 0 0
Ramat Gan
Country [51] 0 0
Israel
State/province [51] 0 0
Zerifin
Country [52] 0 0
Italy
State/province [52] 0 0
Campania
Country [53] 0 0
Italy
State/province [53] 0 0
Emilia-Romagna
Country [54] 0 0
Italy
State/province [54] 0 0
Lazio
Country [55] 0 0
Italy
State/province [55] 0 0
Lombardia
Country [56] 0 0
Italy
State/province [56] 0 0
Piemonte
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Busan Gwang''yeogsi
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Seoul Teugbyeolsi
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Seoul
Country [60] 0 0
New Zealand
State/province [60] 0 0
Christchurch
Country [61] 0 0
Poland
State/province [61] 0 0
Gdynia
Country [62] 0 0
Poland
State/province [62] 0 0
Krakow
Country [63] 0 0
Portugal
State/province [63] 0 0
Lisboa
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Kemerovo
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Moscow
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Nizhny Novgorod
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Omsk
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Saratov
Country [69] 0 0
Russian Federation
State/province [69] 0 0
St. Petersburg
Country [70] 0 0
Singapore
State/province [70] 0 0
Singapore
Country [71] 0 0
Spain
State/province [71] 0 0
Madrid
Country [72] 0 0
Spain
State/province [72] 0 0
Málaga
Country [73] 0 0
Spain
State/province [73] 0 0
Barcelona
Country [74] 0 0
Spain
State/province [74] 0 0
Sevilla
Country [75] 0 0
Spain
State/province [75] 0 0
Valencia
Country [76] 0 0
Sweden
State/province [76] 0 0
Uddevalla
Country [77] 0 0
Turkey
State/province [77] 0 0
Ankara
Country [78] 0 0
Turkey
State/province [78] 0 0
Istanbul
Country [79] 0 0
Turkey
State/province [79] 0 0
Izmir
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Cambridgeshire
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Devon
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Hampshire
Country [83] 0 0
United Kingdom
State/province [83] 0 0
London
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Merseyside
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Surrey
Country [86] 0 0
United Kingdom
State/province [86] 0 0
West Midlands
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Leeds
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Manchester
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Romford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Dreyling M, Morschhauser F, Bouabdallah K, Bron D,... [More Details]