HIV-1 Infection
Conditions
Keywords
HIV-1, Lymphoma, Gene therapy
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
Interventions
DRUGCal-1 (LVsh5/C46) drug product
Autologous CD34+ Haematopoietic Stem/Progenitor Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct
Sponsors
CSL Behring
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
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: 1. 1\. 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) 2. 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) 3. High-risk lymphoma requiring a treatment with combined chemotherapy and autologous stem cell transplantation (ASCT)
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Overall survival | 24 months post-transplant | — |
| Time to restart antiretroviral therapy | 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 |
| Absence of detection of vector-derived Replication competent lentivirus (RCL) | 24 months post-transplant | — |
Countries
France
Outcome results
None listed