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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Cal-1 (LVsh5/C46) drug product

Detailed Description

not provided

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75475
    • Hopital Saint Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cal-1( LVsh5/C46) drug product	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse event post transplant	to evaluate the procedure safety	24 months post-transplant
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	as assessed by the United States national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	24 months post-transplant
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	extent of HSPCtn and Ttn survival as measured by Cal-1 marking and expression in peripheral blood	24 months post-transplant
Time to restart antiretroviral therapy		24 months post-transplant

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: CSL Behring; URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Eric OKSENHENDLER, MD, PhD, Assistance Publique - Hôpitaux de Paris; Study Chair: Marina CAVAZZANA, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): July 28, 2020
• Study Completion (Actual): July 28, 2020

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: HIV-1; Lymphoma; Gene therapy
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma; Pharmaceutical Preparations; Investigative Techniques; Technology, Pharmaceutical; Dosage Forms
• Other Study ID Numbers: P 141004; 2015-004453-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No