A PHASE 2 OPEN LABEL STUDY TO INVESTIGATE THE EFFICACY OF AUTOLOGOUS EBV-SPECIFIC T-CELLS FOR THE TREATMENT OF PATIENTS WITH AGGRESSIVE EXTRANODAL NK/T CELL LYMPHOMA (ENKTCL)
AUTOLOGOUS EBV-SPECIFIC T-CELLS (CMD-003)
The goal of this clinical research study is learn if CMD-003 can help to control non-Hodgkin’s lymphoma. The safety of this drug will also be studied.
Disease Group: Lymphoma
Treatment Agent: AUTOLOGOUS EBV-SPECIFIC T-CELLS (CMD-003)
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Cell Medica, Inc.
Primary Objectives To evaluate the overall response rate per independent endpoint assessment (Measurable disease only) Secondary Objectives • To assess the complete response rate (CR, Measurable disease only) • To assess response duration (Measurable disease only) • To assess time to response (Measurable disease only) • To assess progression free survival (PFS, Measurable disease only) • To assess disease free survival (DFS) • To assess the overall survival (OS) • To assess safety through the incidence of adverse events (AE) Exploratory Objectives • To assess changes in PET-CT SUV scores from baseline. • To assess the plasma and whole blood EBV DNA viral load • To assess EBV-antigen-specific T-cell activity and immunophenotype
IRB Review and Approval Date: 02/19/2015
Recruitment Status: Open
Projected Accrual: 35
1) Screening Phase Selection Criteria: Diagnosis of extranodal NK/T
lymphoma, per World Health Organization (WHO) classification, 4th ed.,
which must include EBV tumor positivity, measured either by EBV encoded
RNA (EBER) or latent membrane protein (LMP)1 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 tosecond CR regardless of previous chemotherapy.
3) Male or female >/= 18 years of age.
4) Weigh >/= 35 kg.
5) Eastern Cooperative Oncology Group (ECOG) performance score 0-2, inclusively
6) Negative beta-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.
9) Treatment Phase Selection Criteria: All Screening Phase inclusion criteria.
10) Documented relapse or progression following at least one prior cycle of an asparaginase-containing chemotherapy regimen.
11) Active disease based on any one of the following present at the baseline study visit orwithin two weeks prior to the baseline study visit: a.Imaging (may use local imaging) b.Clinical sign(s) including skin lesions consistent with lymphoma, organdysfunction or organomegaly not attributable to other causes; or other clinicalsign(s) c.Detectable blood or plasma ENV DNA (may use local laboratory).
12) Completed most recent course of chemotherapy at least 2 weeks prior to first studyproduct dose.
13) Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities asdefined by </= Grade 1 according to NCI CTCAE v4.0. (Transfusion to achieve thehematological criteria is acceptable.)
14) Pulse oximetry of >/= 90% on room air.
1) Screening Phase Selection Criteria: Known central nervous system
2) NK/T cell leukemia.
3) Known hypersensitivity to the investigational product or any components in the final formulation (e.g. dimethyl sulfoxide (DMSO) and/or human serum albumin (HSA)).
4) Positive laboratory test for anti-human immune deficiency virus 1, 2; hepatitis B surface antigen, anti-human T-cell leukemia virus; anti-hepatitis C virus, or syphilis (Patients with anti-hepatitis B core antibody are eligible if negative for hepatitis B surface antigen).
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 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, except for localized basal cell carcinoma of skin, squamouscell carcinoma of the skin or cervical carcinoma in situ.
10) Previous non-hematological malignancy, except for adequately treated basal-cellcarcinoma of skin, squamous cell carcinoma of the skin or cervical carcinoma in-situwithout current evidence of disease, unless the tumor was treated with curative intentmore than 5 years prior to study entry.
11) Any prior allogeneic hematopoietic stem cell transplant.
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 to3 months after end of initial asparaginase based chemotherapy, 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 activityusing the quantitative 5-point Deauville score following initial asparaginase basedchemotherapy 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: d.Class III or IV heart failure as defined by the New York Heart Association, e.Cardiac angioplasty or stenting f.Documented myocardial infarction, or g.Unstable angina.
17) Systemic fungal, bacterial, viral or other infection that is not controlled.
18) Third or greater relapse.
19) Treatment Phase Selection Criteria: All Screening Phase exclusion criteria with the following exception: a.ALC < 400/µL
20) Use of any investigational agents within prior 4 weeks.
21) Radiotherapy within prior 3 weeks.
22) Major surgery within prior 2 weeks.
23) Signs/ symptoms of severe infection within prior 2 weeks.
24) Systemic corticosteroids within 24 hours prior to study product administration.
25) Evidence of hepatic dysfunction based on serum total bilirubin > 3 times upper limit ofnormal (ULN), or ALT > 5 times ULN or AST > 5 times ULN.
Information and next steps
For general questions about clinical trials: