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

NCT03593187 | Completed Phase 1 DMC

• 2 other identifiers: P 1410042015-004453-41
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1 Infection

Keywords

HIV-1; Lymphoma; Gene therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

• 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

Study Arms (1)

Cal-1( LVsh5/C46) drug product

EXPERIMENTAL

Drug: Cal-1 (LVsh5/C46) drug product

Interventions

Cal-1 (LVsh5/C46) drug product DRUG

Autologous CD34+ Haematopoietic Stem/Progenitor Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct

Cal-1( LVsh5/C46) drug product

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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,
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• CSL Behring: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hôpital Saint Louis

Paris, 75475, France

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Marina CAVAZZANA, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

• Eric OKSENHENDLER, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 20, 2018
• Study Start: January 15, 2019
• Primary Completion: July 28, 2020
• Study Completion: July 28, 2020
• Last Updated: November 20, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)