14F7 in chronic B-cell lymphoproliferative syndrome

• Register: RPCEC
• Last refreshed on: 29 April 2024
• Main ID: RPCEC00000266
• Date of registration: 07/03/2018
• Prospective Registration: Yes
• Primary sponsor: Center of Molecular Immunology (CIM)
• Public title: 14F7 in chronic B-cell lymphoproliferative syndrome
• 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
• Date of first enrolment: 30/05/2018
• Target sample size: 142
• Recruitment status: Pending
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000266-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Open. Control group: Dose comparison. Assignment: Other. Purpose: Treatment
• Phase: 1-2

Countries of recruitment

Cuba

Contacts

• Name: Ivis Cristina Mendoza Hernandez
• Affiliation: National Coordinating Center for Clinical Trials (CENCEC)

• Name: Yanelda de los Angeles Garcia Vega
• Affiliation: Center of Molecular Immunology

Key inclusion & exclusion criteria

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).

Age minimum: 18 years
Age maximum: None
Gender: Male/Female

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.

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

Secondary Outcome(s)

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.

Secondary ID(s)

Not applicable

Source(s) of Monetary Support

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

Secondary Sponsor(s)

Not applicable