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: 19.0Level: PTClassification code 10034623Term: Peripheral T-cell lymphoma unspecifiedSystem 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-DE
- Lead Sponsor
- Cell Medica Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
FOR SCREENING PHASE:
1. Diagnosis of extranodal NK/T lymphoma, per WHO classification, 4th ed., which must include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1 immunostaining.
2. a) Clinically suspected or documented relapse/progression, at any time following at least one cycle of an asparaginase-based chemotherapy OR
b) High-risk disease (stage III/IV, KPI groups 3-4 or IPI intermediate-high) at any time (regardless of chemotherapy status and disease relapse/ progression)*
3. Male or female = 18 years of age.
4. Weigh = 35 kg.
5. ECOG performance score 0-2, inclusively.
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.
*Option B is intended to allow for advance manufacture of product in high risk patients to ensure immediate availability at time of relapse.
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. At least one prior cycle of gemcitabine-based salvage chemotherapy, or alternative salvage regimen if patient has previously been treated with gemcitabine or if there is medical rationale for administration of an alternative salvage regimen.
4. a) Presence of measurable disease as defined by at least one of the following:
(i) Revised Response Criteria for Malignant Lymphoma (Cheson 2007)
(ii) The modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
(iii) For patients with skin disease, biopsy confirmation of cutaneous NK/T lymphoma.
(Patients meeting any one of the above criteria will be assigned to Group A), OR
b) No measurable disease (assigned to Arm B).
5. Completed most recent course of chemotherapy at least 2 weeks prior to first study drug dose.
6. 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).
7. Life expectancy = 8 weeks.
8. 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. 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 dose of alternative corticosteroid within 10 days prior to obtaining 100 mL 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 (including hemophagocytic lymphohistiocytosis) 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.
10. Previous non-hematological malignancy, except for adequately treated basal-cell carcinoma of 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 or solid organ transplant.
FOR TREATMENT PHASE:
1. All Screening Phase exclusion criteria.
2. Use of any investigational agents within prior 4 weeks.
3. Radiotherapy within prior 3 weeks.
4. Major surgery within prior 2 weeks.
5. Signs/ symptoms of severe infection within prior 2 weeks.
6. Systemic corticosteroids within 24 hours prior to study drug administration.
7. Symptoms of cardiac failure with New York Heart Association classification of III or IV.
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;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);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 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);Timepoint(s) of evaluation of this end point: Duration of study (up to 2 years after last dose).