A Study Evaluating the Safety of Cal-1 (LVsh5/C46) Drug Product in HIV-1 Infected Patient With High Risk Lymphoma
- Conditions
- HIV-1 Infection
- Interventions
- Drug: Cal-1 (LVsh5/C46) drug product
- Registration Number
- NCT03593187
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
The purpose of this study is to evaluate the safety and the feasibility, and the success of engraftment of the introduction of Cal-1 gene-transduced haematopoietic cell populations (Ttn and HSPCtn) in patients with HIV-1-related high-risk lymphoma.
- Detailed Description
not provided
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2
Eligible subjects will undergo screening assessments at three time points:
- Screening 1 at the beginning of chemotherapy,
- Screening 2 (first "check-point") after the harvest for CD34,
- Screening 3 (second "check-point") before the ASCT procedure. Potential subjects must satisfy all of the inclusion criteria to be enrolled in the study and proceed with the first apheresis (day -39).
In-A. Prior to any study-related procedures, signed informed consent indicating that they understand the purpose, risks and procedures required for the study and are willing to participate in the study In-B. Individuals aged 18 to 60 years of age (inclusive) at time of consent In-C. Women with child-bearing potential must be on adequate effective contraception (continuous progestative contraception) In-D. Documented HIV-1 infection at or before the time of lymphoma diagnosis In-E. Treatment with antiretroviral agents (excluding NNRTI) introduced or optimized at the time of screening
In-F. Biopsy-proven lymphoma meeting one of the following criteria:
-
- Intermediate- or high-grade B-cell non-Hodgkin lymphoma, meeting 1 of the following criteria:
- in first complete remission with high-risk features such as T-cell lymphoma and plasmablastic lymphoma (after multidisciplinary consultation regarding the indication of ASCT in this context). The decision of ASCT is independent of the present clinical trial.
- in partial remission
- relapsed after initial complete remission
- failed induction therapy but responds to salvage therapy (i.e., chemosensitive disease)
-
Hodgkin lymphoma, meeting 1 of the following criteria:
- in first or greater relapse after initial complete remission
- in partial remission
- failed induction therapy but responds to salvage therapy (i.e. chemosensitive disease)
-
High-risk lymphoma requiring a treatment with combined chemotherapy and autologous stem cell transplantation (ASCT)
Ex-A. -Left ventricular ejection fraction <50% at Screening 1:
Ex-B. Abnormal biochemistry at Screening 1:
Alanine and/or aspartate aminotransferase (ALT/AST) >10 x upper limit of normal (ULN) Total bilirubin > 2.5 x ULN Creatinine clearance <60ml/min Ex-C. Severe coagulopathy Ex-D. Prothombin time > 2x ULN Ex-E. Evidence of co-infection with hepatitis B virus (HBsAg+), hepatitis C virus, West Nile Virus, or Human T-lymphotropic virus (HTLV-1) as detected at Screening 1 Ex-F. Stay in West Nile Virus endemic area less than 6 weeks prior to CD34+ collection Ex-G. Evidence of non-treated opportunistic infection during the pre-infusion period Ex-H. Evidence of not-treated CNS involvement of lymphoma at Screening 1 Ex-I. Isolated CNS relapse of the lymphoma without other evidence of active disease at Screening 1 Ex-J. Known hypersensitivity to G-CSF (Neupogen™) or plerixafor (Mozobil™) Ex-K. Evidence of uncontrolled HIV-1 viremia at screening 2 and/or 3 (plasma HIV-1 RNA ≥ 1.000 copies/ml confirmed in 2 successive blood samples) Ex-L. Evidence of chemoresistant lymphoma at screening 2 Ex-M. Any contra-indication to ASCT at any time during the pre-infusion period Ex-N. Participation in any study involving any investigational drug or medical device within 3 months prior to Screening 1 Ex-O. Receipt of a vaccine for HIV-1 or any gene transfer product at any time Ex-P. Subjects who will not accept transfusions of blood products Ex-Q. Pregnant or breast-feeding woman at any time Ex-R. Woman of child-bearing potential not under adequate contraceptive protection at any time Ex-S. Inability to understand and provide informed consent Psychological or psychiatric disability thought to be clinically significant in the opinion of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cal-1( LVsh5/C46) drug product Cal-1 (LVsh5/C46) drug product -
- Primary Outcome Measures
Name Time Method Incidence of adverse event post transplant 24 months post-transplant to evaluate the procedure safety
Success of hematopoietic stem cell engraftment 24 months post-transplant evaluation of Cal-1 marking and expression in peripheral blood subpopulations (monocytes, CD4+ and CD8+ lymphocytes)
- Secondary Outcome Measures
Name Time Method Overall survival 24 months post-transplant Absence of detection of vector-derived Replication competent lentivirus (RCL) 24 months post-transplant Frequency and severity of clinical adverse events 24 months post-transplant as assessed by the United States national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Absence of tropism shift from R5 to dual/mixed or X4 at any point after Day 0 24 months post-transplant Quantify gene transfer efficiency and expression 24 months post-transplant extent of HSPCtn and Ttn survival as measured by Cal-1 marking and expression in peripheral blood
Time to restart antiretroviral therapy 24 months post-transplant
Trial Locations
- Locations (1)
Hôpital Saint Louis
🇫🇷Paris, France