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The Effect of Ixazomib on the Latent HIV Reservoir

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Nathan W. Cummins, M.D., Mayo Clinic
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Nathan W. Cummins, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02946047
First received: October 24, 2016
Last updated: July 13, 2017
Last verified: July 2017
  Purpose
The goal of this study is to determine the safety and tolerability of Ixazomib in HIV infected patients who are on a stable regimen of ART that suppresses HIV replication. A secondary goal is to determine the effect of ixazomib on the size of the HIV reservoir.

Condition Intervention Phase
HIV Drug: Ixazomib Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Pilot Study of Ixazomib to Reduce the Number of HIV DNA Positive Lymphoid Cells

Resource links provided by NLM:


Further study details as provided by Nathan W. Cummins, M.D., Mayo Clinic:

Primary Outcome Measures:
  • Safety [ Time Frame: 7 months ]
    Time to complete one dosing regimen of Ixazomib


Secondary Outcome Measures:
  • Change in cell associated HIV DNA in CD4 T cell subsets [ Time Frame: 26 weeks ]
    HIV copies per million cells

  • Change in culturable HIV by quantitative viral outgrowth assay [ Time Frame: 26 weeks ]
    infectious units per million CD4 T cells

  • Change in absolute CD4 T cell [ Time Frame: 26 weeks ]
    cells per microliter

  • Change in absolute CD8 T cell count [ Time Frame: 26 weeks ]
    cells per microliter

  • Change in CD4/CD8 T cell count ratio [ Time Frame: 26 weeks ]
    Total percentage


Estimated Enrollment: 17
Actual Study Start Date: March 20, 2017
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment group
Patients will be given at least one treatment cycle of Ixazomib.
Drug: Ixazomib
Patients Will be given oral Ixazomib on days 1, 8 and 15 of a 28 day cycle. Additional cycles, dosing days may be added and dose increased based on patient tolerability.
Other Name: Ninlaro

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The following laboratory values obtained <=14 days prior to registration.
  • ANC ≥ LLN (lower limit of normal) and ≤ULN (upper limit of normal), Hgb ≥ LLN and ≤ULN, PLT ≥ LLN and ≤ULN
  • Total bilirubin ≤ULN and the direct bilirubin must be ≤ ULN; AST <1.5 x ULN and ALT <1.5 x ULN
  • Creatinine <2.0 x ULN and an estimated creatinine clearance > 60 ml/min
  • HIV infection with suppressed viral replication on at least 3 active drug ART for at least 6 months
  • Suppressed viral replication is defined by plasma HIV viral load <20copies/mL.
  • Patient must have HIV viral load <20 copies/ml on two occasions at least 3 months apart.
  • In the opinion of the treating physician, patients must have available other regimens likely to suppress HIV should their current regimen fail.
  • Male or female patients age >=18 years
  • A plasma HIV RNA viral load demonstrating a measure of <20 copies/mL within 30 days prior to study initiation.
  • CD4 count >500 cells/mm3 within 30 days prior to study enrollment
  • Females must have a negative pregnancy test prior to receiving the 1st dose of ixazomib and be postmenopausal for at least 1 year before the screen visit, or surgically sterile,
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception AND a second method of contraception for female partners of childbearing potential during the entire study treatment period and through 90 days after the last dose of ixazomib,
    • OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
    • AND
    • Agree to forego sperm donation for the same period as above.

Exclusion Criteria:

  • The following laboratory values obtained <=14 days prior to registration.

    • ANC < LLN and >ULN, Hgb < LLN and >ULN, PLT < LLN and >ULN
    • Total bilirubin >ULN or the direct bilirubin is > ULN; AST >1.5 x ULN or AST >1.5 x ULN
    • Creatinine >=2.0 x ULN or an estimated creatinine clearance <=60mL/min
  • Diagnosed and treated for a malignancy within 5 years before randomization, or previously diagnosed with a malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any infection except HIV (excluding benign conditions that is unlikely to be affected or modulated by treatment with ixazomib, e.g. stye or furuncle), or treatment with anti-infective agents within 14 days of enrollment.
  • Pregnant women
  • Women of childbearing potential and Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking the drug and for 90 days after stopping ixazomib.
  • Any history of peripheral neuropathy, or peripheral neuropathy detected during the screening period.
  • Major surgery within 14 days before study registration
  • Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
  • Evidence of current uncontrolled cardiovascular conditions, including serious cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
  • QTc > 450 milliseconds (msec) for men and >470 milliseconds for women (83) on a 12 lead ECG obtained during the Screening period.
  • Known hepatitis B DNA positive status and/or HBsAg positive and/or HBeAg positive, or active hepatitis C replication (HCV RNA positive) or currently on hepatitis C treatment.
  • Known history of cirrhosis or active liver inflammation, including "fatty liver" or non-alcohol steatohepatitis (NASH).
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known allergy to any of the study medications, their analogues or excipients in the various formulations.
  • Any other recent or concurrent medical condition that, in the Investigator's opinion, would impose any risk to the patient
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02946047

Contacts
Contact: James Allen 507-255-9899 allen.james1@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: James Allen    507-255-9899    allen.james1@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Takeda
Investigators
Principal Investigator: Nathan Cummins, MD Mayo Clinic
  More Information

Responsible Party: Nathan W. Cummins, M.D., MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02946047     History of Changes
Other Study ID Numbers: 16-001938
Study First Received: October 24, 2016
Last Updated: July 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nathan W. Cummins, M.D., Mayo Clinic:
HIV
ART
Antiretroviral
Therapy
Reservoir
Cure

Additional relevant MeSH terms:
Ixazomib
Glycine
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2017