14F7 in chronic B-cell lymphoproliferative syndrome

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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.

Acronym of Public Title:

14F7-CLPS

Scientific title:

Phase I / II study of dose escalation and expansion to cohorts, with the therapeutic antibody 14F7h (Anti-NGlicolilGM3) in patients with chronic B-cell lymphoproliferative syndrome, refractory or relapsing

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)

Reference number:

In process

Principal investigator

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

First name:

Julio

Midle name:

Damaso

Last name:

Fernandez Aguila

Medical Specialty :

Second Degree Specialist in Hematology

Affiliation:

Gustavo Aledereguia Lima Hospital

Postal address:

Calle 51 A y Avenida 5 de Septiembre

City:

Cienfuegos

País:

Cuba

Zip Code:

55100

Telephone:

+53-043591792

Email address:

jfernandez@gal.sld.cu

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:

Villa Clara, Arnaldo Milian Castro, Agnerys Lopez Sacerio, MD. 1st Degree Specialist Hematology

Havana, Hermanos Ameijeiras, Kali Cepero LLauger, MD. 1st Degree Specialist Hematology

Havana, Hematology and Immunology Institute, Yusleidy Concepcion Fernandez, MD. 1st Degree Specialist Hematology

Sancti Spiritus, Camilo Cienfuegos, Gloritza Rodriguez Matos, MD. 1st Degree Specialist Hematology

Research ethics committees:

Gustavo Aldereguia Lima, 11/08/2017

Arnaldo Milian Castro, 11/10/2017

Hermanos Ameijeiras, 19/10/2017

Hematology and Immunology Institute, 24/11/2017

Camilo Cienfuegos, 30/11/2017

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

30/05/2018

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:

Non-Hodgkin lymphoma, Chronic lymphocytic leukemia, Multiple myeloma

Intervention(s):

Stage I 14F mAb intravenously in 5 dose levels (25 mg, 50 mg, 100 mg, 200 mg o 400 mg) every 15 days (5 doses) in induction period and, then every 28 days (4 doses) in maintenance period. Stage II 14F mAb intravenously in 2 dose level for each cohort of patients according to health condition. One dose level will be the Maximum Tolerable Dose (MTD) obtained in stage I and, the other dose level will be the immediate dose lower or higher than MTD according to the criteria of the protocol. Both dose levels will be administered in the same scheme as stage I.

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):

Stage I Serious Adverse Events (SAE) with causality relationship (Serious Adverse Events those that: 1. Produce death, 2. life-threatening, 3. hospitalization or prolongation of hospitalization indicated, 4. Produce disability / persistent or significant disability, 5. Produce birth defect or congenital anomaly. Will be consider causality relationship when the SAE has definitive/highly probable or probable causality relationship). Measuring time: during and after each administration, throughout the study period until week 52. Stage II Objective response (Complete response y partial response according to the international criteria for each chronic B-cell lymphoproliferative syndrome). Measurement time: weeks 13, 29, 41 and 52

Key secondary outcomes:

Control of the disease (It will to evaluate according to the International response criteria for each chronic B-cell lymphoproliferative syndrome (CLPS) in the categories "Control of the disease" (complete + partial response + stable disease) and "Non-responders" (death + progressive disease) . Measurement time: weeks 13, 29, 41 and 52. Relapse-Free Survival (The time from the date of achievement of a complete response until the date of relapse or death from any cause. Defined only for patients achieving complete response). Measuring time: 52 weeks Event-free survival (The time from treatment began until treatment failure, or relapse or death from any cause). Measurement time: 52 weeks Progression free survival (The time from the start of treatment until to the date of disease progression or death from any cause) Measurement time: 29 and 52 weeks Survival rates (Percentage of patients alive from the diagnosis and the start of treatment). Measuring time: week 29 and week 52 Time to progression (Time measured from the start of treatment to the date of disease progression). Measurement time: 52 weeks Time to treatment failure (Time from the start of treatment to the interruption of treatment for any reason, including disease progression, toxicity or death). Measurement time: 52 weeks Immunogenicity HAHA response (Yes, No. It will be "Yes" when the value of the density of the patient serum is greater than 2 standard deviations of the value of the sera of healthy donor). Measurement time: At baseline, prior to each administration of product, week 29 and week 52. Pharmacokinetics Bioavailability of mAb 14F7hT (numerical value). Measurement time: 1st and 5th administration Volume of distribution of the MAb 14F7hT (numerical value). Measurement time: 1st and 5th administration Constant of elimination of the AcM 14F7hT (numerical value). Measurement time: 1st and 5th administration Maximum concentration of mAb 14F7hT (numerical value). Measurement time: 1st and 5th administration Average life time of the mAb 14F7hT (numerical value). Measurement time: 1st and 5th administration Plasma clearance of mAb 14F7hT (numerical value). Measurement time: 1st and 5th administration Others Expression of surface markers specific to B cells (Percent of expression of markers). Measurement time: at baseline, week13 and week 29 Expression of ganglioside NGGM3 (Negative, weak staining, moderate staining or intense staining). Measurement time: At baseline and, week 29 Safety Adverse Events-AE (Occurrence of any AE (Yes, No), Description (name of AE), duration (Time from the event start until its termination), intensity (Mild, Moderate, Severe, AE that threatens or incapacitates and AE that produces death according to the Common Toxicity Criteria-CTCAE version 4.0 of the National Cancer Institute of the United States), Seriousness (Serious or Not applicable (NA) when the AE is not serious), result (recovered, improved, persists, sequelae), attitude towards treatment (no changes, dose modification, temporary or definitive interruption of treatment under study), causality relationship (Definitive, Very Likely, Probable, Possible, Not related, Unknown), Product Batch (number of the batch used)). Measurement time: In each administration of the product and up to 30 days after the last dose of the product is administered Results of laboratory tests (hematology, blood chemistry and urine). Measurement time: At baseline, weeks 13, 29, 41 and 52. Vital signs (Blood pressure in mmHg, Heart rate in minutes, Temperature in Celsius degrees). In each product administration. Result of the physical examination (It will be evaluated by systems, in Normal or Abnormal, depending on the findings, the category not examined will be used, in case it is not done). Measurement time: At baseline, in each administration of the product and in week 52.

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:

None

Inclusion criteria:

1. Refractory or relapsing B-cell cell lymphoproliferative syndrome, ganglioside NGlicolilGM3 (NGGM3) positive. 2. Age ≥18 years, any gender and race. 3. ECOG ≤ 3. 4. Life expectancy of 6 months. 5. No candidates for transplant of hematopoietic progenitors or immunochemotherapy schemes not previously used. 6. Four or more weeks from the previous specific therapy (QT, RT, biological therapies) (applicable to patients’ refractory to the previous treatment). 7. Patients with laboratory parameters as detailed below: Hemoglobin ≥ 80 g / L, Absolute neutrophil count ≥ 1.5 x 109 / L, Platelet count ≥ 75 x 109 / L, Liver function (bilirubin, ASAT or ALAT ≤ 2.5 times the normal reference range of each institution), Renal function preserved (creatinine clearance ≥45 mL / min according to the Cockcroft and Gault formula). 8. Voluntary signature of the informed consent model. 9. Subjects of childbearing age and sexually active should agree to use a method of contraception during treatment (criteria valid only for patients of childbearing age).

Exclusion criteria:

1. Pregnant, puerperal or breastfeeding 2. Cytopenia of uncontrolled immune cause 3. Active infection or known positivity for HIV, hepatitis B or C virus 4. Heart failure grade III / IV according to NYHA criteria (New York Heart Association) 5. Chronic decompensated diseases such as: arterial hypertension, diabetes mellitus, ischemic cardiopathy or other symptomatic cardiovascular diseases, epilepsy, obstructive pulmonary disease. 6. Acute allergic states or known hypersensitivity to any component of the formulation under study. 7. Obvious mental disability or other limitation that prevents the patient from signing their consent or hinders the evaluation of the study. 8. Being receiving another research product. 9. Another clinically active neoplasm that needs specific treatment (except basal cell carcinomas or cutaneous carcinomas in situ).

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:

Randomized controlled trial

Masking:

Open

Control group:

Dose comparison

Study design:

Other

Other design:

Dose scale-up (Study in two stages. Stage I: dose escalation and Stage II: basket type design with randomization at two dose levels in 3 patient cohorts)

Phase:

1-2

Target sample size:

142

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

Middle Name:

Cristina

Last Name:

Mendoza Hernandez

Specialty:

Bachelor in Pharmaceutical Sciences. Master in Clinical Pharmacology

Affiliation:

National Coordinating Center for Clinical Trials (CENCEC)

Postal Address:

5ta A / 60 y 62 Playa

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+53-72164227

Email :

ivis@cencec.sld.cu

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

Middle Name:

de los Angeles

Last Name:

Garcia Vega

Specialty:

Bachelor in Biochemistry. Master in Clinical Laboratory Sciences

Affiliation:

Center of Molecular Immunology

Postal Address:

216 & 15, Atabey, Playa

City:

Havana

País:

Cuba

Zip Code:

16040

Telephone:

+53-72717933 Ext 3397

Email :

yaneldag@cim.sld.cu

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:

RPCEC00000266

Date of Registration in Primary Registry:

07/03/2018

Record Verification Date:

2018/03/07

Next update date:

2019/03/07

Link to the spanish version:

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14F7 in chronic B-cell lymphoproliferative syndrome

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