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

• ClinicalTrials.gov Identifier: NCT02486510
• Recruitment Status: Terminated
• First Posted: July 1, 2015
• Last Update Posted: December 18, 2015
• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Information provided by (Responsible Party): Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: Maraviroc	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Cytoreductive Chemotherapy and a CCR5 Coreceptor Antagonist on HIV-1 Eradication
• Study Start Date: July 2012
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

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 Name: Celsentri

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Spain

Hospital Universitario Ramon Y Cajal

Madrid, Spain, 28034

Hospital Universitario La Paz

Madrid, Spain, 28046

Sponsors and Collaborators

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

More Information

Publications:

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.

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.

• Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• ClinicalTrials.gov Identifier: NCT02486510
• Other Study ID Numbers: CHEMOMAR
• First Posted: July 1, 2015
• Last Update Posted: December 18, 2015
• Last Verified: December 2015

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

HIV-1; CCR5 coreceptors; Maraviroc

Additional relevant MeSH terms:

Maraviroc; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; CCR5 Receptor Antagonists