A Study Evaluating the Safety of Cal-1 (LVsh5/C46) Drug Product in HIV-1 Infected Patient With High Risk Lymphoma

HIV-1 Infection Clinical Trial

— GENHIV  

Official title:

A Phase I/II Study of the Safety of CD34+ Haematopoietic Stem/Progenitor Cells and CD4+ T Lymphocytes Transduced With LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct, in HIV-1 Infected Patients With High-risk Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03593187
• Other study ID #: P 141004
• Secondary ID: 2015-004453-41
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 15, 2019
• Est. completion date: July 28, 2020

Study information

• Verified date: November 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

not provided

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: July 28, 2020
• Est. primary completion date: July 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1 Infection
• Lymphoma

Intervention

Drug:
• Cal-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

Locations

Country	Name	City	State
France	Hôpital Saint Louis	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	CSL Behring

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse event post transplant	to evaluate the procedure safety	24 months post-transplant
Primary	Success of hematopoietic stem cell engraftment	evaluation of Cal-1 marking and expression in peripheral blood subpopulations (monocytes, CD4+ and CD8+ lymphocytes)	24 months post-transplant
Secondary	Overall survival		24 months post-transplant
Secondary	Absence of detection of vector-derived Replication competent lentivirus (RCL)		24 months post-transplant
Secondary	Frequency and severity of clinical adverse events	as assessed by the United States national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	24 months post-transplant
Secondary	Absence of tropism shift from R5 to dual/mixed or X4 at any point after Day 0		24 months post-transplant
Secondary	Quantify gene transfer efficiency and expression	extent of HSPCtn and Ttn survival as measured by Cal-1 marking and expression in peripheral blood	24 months post-transplant
Secondary	Time to restart antiretroviral therapy		24 months post-transplant