1B8 vs MabThera® in patients with Diffuse large B-cell lymphoma

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Pharmacokinetics and safety of 1B8 vs MabThera evaluation, both in combination with CHOP chemotherapy in newly diagnosed patients diffuse large B-cell lymphoma, CD 20+. Phase I.

Secondary indentifying numbers:

Not applicable

Issuing authority of the secondary identifying numbers:

Not applicable

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM) Ministry of Public Health (MINSAP)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

19/08/2016

Reference number:

B-17-058-L01

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Elias, INOR Calixto, HHA

Last name:

Gracia Medina, INOR Hernandez Cruz, HHA

Medical Specialty :

MD. Second degree specialist in Oncology, INOR MD. Second degree specialist in Hematology, HHA

Affiliation:

Havana, National Institute of Oncology and Radiobiology (INOR) Havana, “Hermanos Ameijeiras” Hospital (HHA)

Postal address:

29 esq F, Vedado, Plaza de la Revolucion, INOR San Lazaro No. 701 esq. Belascoain. Centro Habana, HHA

City:

Havana, INOR Havana, HHA

País:

Cuba, INOR Cuba, HHA

Zip Code:

10400, INOR 10300, HHA

Telephone:

+53-78369209

+53-78761459

Email address:

oncmedica@inor.sld.cu [1]

hemat@hha.sld.cu [2]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana, Hematology and Immunology Institute, Yamile Quintero Sierra, MD, first degree specialist in Hematology

Research ethics committees:

National Institute of Oncology and Radiobiology, May 26, 2016.

Hermanos Ameijeiras Hospital, May 10, 2016.

Hematology and Immunology Institute, May 20, 2016.

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Recruiting

Date of first enrollment:

26/04/2017

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Diffuse large B-cell lymphoma, newly diagnosed

Health condition(s) code:

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Hemic and Lymphatic Diseases

Immunoproliferative Disorders

Immune System Diseases

Neoplasms

Intervention(s):

Group A (Experimental): 1B8 (Rituximab biosimilar) 375 mg/m2 every 21 days (Intravenous infusions) + CHOP scheme for 6 to 8 cycles. Group B (Control) MabThera (RITUXAN) 375mg / m2 every 21 days (Intravenous infusions) + CHOP scheme for 6 to 8 cycles. CHOP scheme: Doxorubicin (50 mg/m2 day 1); Vincristine (1.4 mg/m2 day 1); Cyclophosphamide (750 mg/m2 day 1); Prednisolone (100 mg days 1 to 5). It is will administered every 21 days, depending on the patient's clinical condition and response to treatment, up to a maximum of 6-8 cycles, considering a maximum cumulative dose of doxorubicin of 450 mg / m2.

Intervention code:

Rituximab

Antibodies, Monoclonal, Murine-Derived

Antibodies, Monoclonal

Biosimilar Pharmaceuticals

Administration, Intravenous

Doxorubicin

Vincristine

Cyclophosphamide

Prednisone

Intervention keyword:

1B8 RITUXAN MabThera® Rituximab biosimilar CHOP scheme

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

- Pharmacokinetic Serum concentration (Cp). Measurement time: before each cycle of treatment and 3 months after the last cycle Maximum concentration (AUC). Measurement time: before each cycle of treatment and 3 months after the last cycle Half-life (t ½). Measurement time: before each cycle of treatment and 3 months after the last cycle Plasma clearance (CL). Measurement time: before each cycle of treatment and 3 months after the last cycle - Pharmacodynamic - B cells depletion (Absolute counts of CD19+ in peripheral blood). Measurement time: before each cycle of treatment and 3 months after the last cycle

Key secondary outcomes:

Effect: Clinical Response (standardized criteria for NHL: complete remission, unconfirmed complete response, partial remission, stable disease or progressive disease). Measurement time: 4 weeks after the last cycle of treatment Safety: Adverse events (AEs). Measurement time: 10 months - Occurrence of an AE in the subject (yes / no) - Description of AE (Name of adverse event) - Duration of AE (difference between the start dates and completion of the event) - Intensity AE (Mild, Moderate, Severe, Life-threatening or disabling, produces death) - Gravity AE (Severe / serious, severe / not serious) - Attitude to study treatment (unchanged, dose modification, temporary interruption or discontinuation of study treatment) - Result of the AE (recovered, improved, persists or sequels) - Causal relationship (1 Definitive, 2. Very Probable, 3. Probable, 4. Possible 5. Not related 6. Unknown) Immunogenicity: HACA Response (according OD title). Measurement time: before each cycle of treatment, 4 weeks post the last cycle of treatment and 3 months after the last cycle

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

70 years

Inclusion criteria:

1. Patients that fulfill diagnosis criteria 2. Eligible for scheme CHOP 3. Age greater than or equal to 18 years and not older than 70 years, of any gender. 4. ECOG performance status less than or equal to 2 5. Express written request of the patient 6. Measurable disease at diagnosis 7. Requirements of the clinical laboratory (Hb≥ 100 g/L, ALC ≥ 3 x 109 cells/L, ANC ≥ 1,5x109 /L, Platelets ≥100 x 109/L, Transaminases ≤ 2.5 time upper limit of normal, Creatinine and bilirubin ≤ 1.5 upper limit of normal)

Exclusion criteria:

1. LNH evidence of spread of the central nervous system or primary CNS involvement 2. Extranodal NHL, intravascular or plasmablastic 3. Uncontrolled hypertension 4. History of Demyelinating disease or inflammatory of the CNS or peripheral 5. Pregnancy or breastfeeding. 6. Human Immunodeficiency Virus (HIV) seropositivity 7. History of other cancer, except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix. 8. Acute allergy or history of severe allergic reactions or autoimmune disease or primary immunodeficiencies 9. On any other experimental product. 10. History of allergy to active substances, excipients and murine proteins similar to the experimental product or any of the drugs chemotherapy regimen that will receive to the patient 11. Decompensated related chronic disease, they are including but not limited to: active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, aortic stenosis, endocarditis and psychiatric diseases that may limit adherence to the requirements of the assay 12. Left Ventricular Ejection Fraction less than 50% 13. Known seropositive for hepatitis B or C virus

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Non-randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

Target sample size:

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Ivis

Last Name:

Mendoza Hernandez

Specialty:

Degree in Pharmaceutical Sciences. Master in Clinical Pharmacology

Affiliation:

National Coordinator Center for Clinical Trials

Postal Address:

5ta A e/ 60 y 62, Playa

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+537-216-4227 +537-2164 228

Email :

ivis@cencec.sld.cu [3]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Yanelda

Last Name:

Garcia Vega

Specialty:

Degree in Biochemistry. Master of Science in Clinical Laboratory

Affiliation:

Center of Molecular Immunology

Postal Address:

216 Esquina 15, Atabey, Playa

City:

Havana

País:

Cuba

Zip Code:

16040

Telephone:

+537 2717933 Ext 3449

Email :

yaneldag@cim.sld.cu [4]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000216

Date of Registration in Primary Registry:

01/09/2016

Record Verification Date:

2018/02/19

Next update date:

2019/02/19

Link to the spanish version:

Click here [5]