A clinical trial to investigate how well a product containing certain immune cells (EBV-specific T-cells) manufactured from the patient's own blood cells works in the treatment of patients with a rare type of non-Hodgkin's lymphoma (aggressive extranodal NK/T-cells lymphoma).
- Conditions
- Aggressive EBV positive extranodal NK/T-cell lymphoma (ENKTCL)MedDRA version: 19.0 Level: PT Classification code 10034623 Term: Peripheral T-cell lymphoma unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2013-004380-31-GB
- Lead Sponsor
- Cell Medica Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
FOR SCREENING PHASE:
1. Diagnosis of extranodal NK/T lymphoma, per WHO classification, which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining.
2. a) Active Disease:
(1) Clinically suspected or documented relapse/progression, in first or second relapse following at least one cycle of an asparaginase-based chemotherapy regimen OR
2) Initial disease or first or second relapse and unable to tolerate one full cycle of asparaginase-based chemotherapy regimen OR
b) High-risk disease (stage III/IV, KPI groups 3-4 or IPI intermediate-high) prior to second CR regardless of previous chemotherapy (Appendix B)
3. Male or female = 18 years of age.
4. Weigh = 35 kg.
5. ECOG performance score 0-2, inclusively (Appendix A).
6. Negative ß-hCG test in women of childbearing potential.
7. Able to understand and comply with the requirements of the study and to provide written informed consent.
8. Estimated life expectancy greater than four months.
FOR TREATMENT PHASE:
1. All Screening Phase inclusion criteria.
2. Documented relapse or progression following at least one prior cycle of an asparaginase-containing chemotherapy regimen.
3. Active disease based on any one of the following present at the baseline study visit or within two weeks prior to the baseline study visit:
a. Imaging (may use local imaging)
b. Clinical sign(s) including skin lesions consistent with lymphoma, organ dysfunction or organomegaly not attributable to other causes; or other clinical signs.
c. Detectable blood or plasma EBV DNA (may use local laboratory)
4. Completed most recent course of chemotherapy at least 2 weeks prior to first study product dose.
5. Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities as defined by = Grade 1 according to NCI CTCAE v4.0. (Transfusion to achieve the hematological criteria is acceptable.)
6. Pulse oximetry of = 90% on room air.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
FOR SCREENING PHASE:
1. Known central nervous system (CNS) lymphoma.
2. NK/T cell leukemia.
3. Known hypersensitivity to the investigational product or any components in the final formulation (e.g. DMSO and/or HSA).
4. Positive laboratory test for anti-HIV 1, 2; HBsAg, anti-HTLV-I; anti-HCV, or syphilis (Patients with anti-hepatitis B core antibody are eligible if negative for HBsAg).
5. Use of systemic corticosteroids >0.5 mg/kg/day prednisolone or equivalent alternative corticosteroid within 10 days prior to obtaining 200 mL whole blood starting material.
6. Patient is pregnant or lactating.
7. Female patients of childbearing potential and male patients with partners of childbearing potential unwilling to use a highly effective method of birth control during the study and for 6 months after the study treatment is concluded.
8. Clinically significant medical condition e.g. pulmonary, neurological, cardiovascular, metabolic, or hematologic that could jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.
9. Active second malignancy, except for localized basal cell carcinoma of skin, squamous cell carcinoma of the skin or cervical carcinoma in situ.
10. Previous non-hematological malignancy, except for adequately treated basal-cell carcinoma of skin, a squamous cell carcinoma of the skin or cervical carcinoma in situ without current evidence of disease, unless the tumor was treated with curative intent more than 5 years prior to study entry.
11. Any prior allogeneic hematopoietic stem cell.
12. Any prior solid organ transplant.
13. Asparaginase-refractory disease, defined by any one of the following:
a. Progression at any time during initial asparaginase-based chemotherapy and up to 3 months after end of initial asparaginase-based chemotherapy regimen; OR
b. Failure to achieve at least PR with initial asparaginase-based chemotherapy, OR
c. Persistence of significant (score 4 or 5) residual FDG-avid metabolic activity using the quantitative 5-point Deauville score following initial asparaginase based chemotherapy regimen.
14. Absolute lymphocyte count (ALC) <400/µL.
15. Any previous autologous EBV specific T cell treatment.
16. History of any one of the following cardiovascular conditions within the past 3 months:
a. Class III or IV heart failure as defined by the New York Heart Association.
b. Cardiac angioplasty or stenting
c. Documented myocardial infarction, or
d. Unstable angina.
17. Systemic fungal, bacterial, viral or other infection that is not controlled
18. Third or greater relapse
FOR TREATMENT PHASE:
1. All Screening Phase exclusion criteria with following exception:
a. ALC < 400/µL.
2. Use of any investigational agents within prior 4 weeks.
3. Radiotherapy within prior 3 weeks.
4. Major surgery within prior 2 weeks.
5.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the overall response rate per independent endpoint assessment;<br> Secondary Objective: To assess the complete response rate (CR)<br> To assess response duration<br> To assess time to response<br> To assess progression free survival (PFS)<br> To assess disease free survival (DFS)<br> To assess the overall survival (OS)<br> To assess safety through the incidence of adverse events (AE)<br> ;Primary end point(s): Overall response rate, defined as best observed response (CR or PR) (Group A only) ;Timepoint(s) of evaluation of this end point: Tumour response will be measured at day 60, day 180, day 270 and day 365.
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): Complete response rate (CR) (Group A only)<br> Response duration (Group A only)<br> Time to response (Group A only)<br> Progression free survival (PFS) (Group A only)<br> Disease free survival (DFS)<br> Overall Survival (OS)<br> Adverse Events (AEs)<br> ;Timepoint(s) of evaluation of this end point: Duration of study (up to 2 years after last dose).