Effect of Cytoreductive Chemotherapy and a CCR5 Coreceptor Antagonist on HIV-1 Eradication (CHEMOMAR)

Effect on HIV-1 cell reservoirs of the concomitant administration of intensive chemotherapy and the pharmacological blockade of CCR5 coreceptors: a pilot, open, randomized, and controlled clinical trial.

Study Overview

• Status: Terminated
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Maraviroc

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who give written consent to participate in the study
• Age between 18 and 65 years old, included.
• Chronic HIV-1 Demonstration of R5 viral tropism (use of CCR5 coreceptors) by genotyping in plasma samples stored
• Patients that are to be treated with intensive chemotherapy for non Hodgkin lymphoma With or without stable antiretroviral therapy
• Patients that are able to understand the purpose of the study and be available for scheduled appointments.
• Both in the case of female and male patients, the patient agrees to use a double barrier method of contraception from the moment of signing the informed consent until 3 months after the end of their participation in the study.

Exclusion Criteria:

• To have planned antiretroviral treatment interruption during the participation in the study
• Hypersensitivity to products used in this study
• To be involved in another clinical trial or received an investigational drug within 3 months prior to the study initiation
• To have contraindications or limitations to perform leukapheresis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1 (Control); Patients receiving intensive chemotherapy with/without stable antiretroviral therapy. Patients not receiving antiretroviral therapy will start it. Patients randomized to this group will not receive clinical trial treatment (neither Maraviroc or Placebo)
Experimental: Group 2 (Treatment); Patients receiving intensive chemotherapy with/without stable antiretroviral therapy and Maraviroc. Patients not receiving antiretroviral therapy will start this theraphy together with Maraviroc.	Drug: Maraviroc; Patients randomized to experimental control will start Maraviroc treatment before, during and after chemotherapy until lymphocytes level recovery. Maraviroc Dose: 300 mg/12 hours For patients receiving an HIV-protease inhibitor (except tipranavir or Fosamprenavir), the dose will be reduced to 150 mg/12hours For patients receiving Efavirenz dose the dose will be 600 mg/12hours; Other Names: Celsentri

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of resting memory CD4+ T cells latently infected with replicative HIV-1, expressed as IUPM	Primary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels	Same as chemotherapy treatment (expected average of 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proviral DNA (copies/million cells)	Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels	Same as chemotherapy treatment (expected average of 6 months)
Effector T cells producing HIV-1 specific gamma interferon (cells/mm3)	Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels	Same as chemotherapy treatment (expected average of 6 months)
Levels of HIV-1 antibodies	Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels	Same as chemotherapy treatment (expected average of 6 months)
Percentage of CD4+ and CD8+ cells with immune activation markers	Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels	Same as chemotherapy treatment (expected average of 6 months)

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Publications and helpful links

General Publications

• Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.
• Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.
• Wang C, Vlahov D, Galai N, Bareta J, Strathdee SA, Nelson KE, Sterling TR. Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy. J Infect Dis. 2004 Sep 15;190(6):1046-54. doi: 10.1086/422848. Epub 2004 Aug 17.
• Moreno S, Mocroft A, Monforte Ad. Medical and societal consequences of late presentation. Antivir Ther. 2010;15 Suppl 1:9-15. doi: 10.3851/IMP1523.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: HIV-1; Maraviroc; CCR5 coreceptors
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: CHEMOMAR