Cidofovir Instillation in Hematopoietic Stem Cell Transplant (HSCT) Recipients With Hemorrhagic Cystitis

Condition(s) targeted: Cystitis; Bladder Diseases

Intervention: Cidofovir (Drug)

Phase: N/A

Status: Not yet recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Roy F. Chemaly, MD, MPH, MBA, Principal Investigator, Affiliation: UT MD Anderson Cancer Center

Overall contact:
Roy F. Chemaly, MD, MPH, MBA, Phone: 713-792-6830

Objectives:

- To determine the systemic absorption of cidofovir administered via bladder

instillation.

- To study the pharmacokinetics of this single dosage regimen of cidofovir administered

via bladder instillation.

- To determine the safety and tolerability of a single dose of 5 mg/kg of cidofovir

administered via bladder instillation.

Official title: Intravesical Cidofovir Instillation in HSCT Recipients With Hemorrhagic Cystitis: A Single Dose Pharmacokinetic Study

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Systemic Absorption of Cidofovir via bladder instillation

Detailed description: The Study Drug:

Cidofovir is designed to fight CMV (a viral infection) by blocking the CMV cells from dividing.

Cidofovir is commonly given by injection. For research purposes, in this study it will be given directly into the bladder through a foley catheter. This is one of the first studies where cidofovir is being given this way in humans.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).

Your medical history will be recorded. Urine and blood (1-2 teaspoons) will be collected for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children. To take part in this study, the pregnancy test must be negative.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other options will be discussed with you.

Study Drug Administration:

If you are found to be eligible to take part in this study, on Day 1, Cidofovir will be put into your bladder through your foley catheter. The catheter will be clamped for 2 hours to keep the drug in your bladder. After 2 hours, the catheter will be unclamped. If you were receiving bladder irrigation as therapy for your hemorrhagic cystitis, this will be restarted.

Study Tests on Day 1:

On the day you receive cidofovir, blood (about 2 teaspoons) will be drawn 6 times. The first blood draw will occur before the cidofovir dose, and the last blood draw will occur 24 hours (+/- 1 hour) after the start of the dose. This blood will be used for pharmacokinetic (PK) and pharmacodynamic (PD) testing. PK testing measures the amount of study drug in the body at different time points. PD testing is used to look at how the level of study drug in your body may affect the disease.

Viral Load Testing:

During this study, extra urine and leftover blood to be collected and used for research to test for certain viruses. These viruses include the type of infection you had when joining this study, as well as cytomegalovirus (CMV) and another type of herpes virus.

The urine samples will be collected before the cidofovir dose on Day 1, after the cidofovir dose on Day 1, and again on Day 4.

Any blood left over from Day 1 testing will also be used for viral load testing.

It is possible that these urine and/or blood samples will be sent to an outside lab to perform this testing. If that occurs, your name and any personal identifying information will be coded before the samples are sent. Coding the samples is designed to protect your privacy.

Follow-Up Tests:

Blood (about 2 teaspoons) will be drawn for routine tests 2 times during the week after your cidofovir dose.

On Day 7 (+/- 2 days), you will be checked for any side effects that could be related to the study drug.

In addition, on Day 14 (+/- 2 days), blood samples will be drawn for PK testing, urine will be collected for routine tests, and your safety data will be recorded.

One final follow-up visit will take place on Day 30 (+/- 2 days). During this visit, the study staff will record any serious side effects you may be experiencing.

Length of Study Participation:

Your active study participation will be over after the Day 7 follow-up visit (+/- 2 days). If you experienced a side effect, however, the study staff will continue checking your medical records until the side effect becomes stable or gets better.

This is an investigational study. Cidofovir given by injection is commercially available and FDA approved to treat CMV in patients with HIV. It is investigational to give cidofovir directly into the bladder of patients who have a viral infection causing bleeding in the bladder.

Up to 6 patients will take part in this study. All will be enrolled at M. D. Anderson.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Polyoma BK or adenovirus viruria has been established either by positive urine cytology or by PCR for BK virus or by positive urine and/or blood culture for adenovirus

2. The patient has either gross hematuria and/or passes blood clots

3. Signed informed consent form

4. Hospitalized patients with a Foley catheter

5. Women of childbearing potential must agree to use 2 acceptable methods of birth control (e. g., abstinence, IUD, or barrier method), during the study period and one for a period of 2 months afterward. At least one of the methods must be a barrier method. Males must also agree to use acceptable method of birth control (barrier method) during the study period and for 2 months afterward.

Exclusion Criteria:

1. Serum creatinine >1. 5 mg/dl and/or calculated creatinine clearance < 55 ml/min using the Cockcroft-Gault Creatinine Clearance formula (CrCl). CrCl = {(140-Age) x Weight (kgs) x 0. 85 (if female)}/ {72x Serum Creatinine (mg/dl)}

2. Urine protein > 100 mg/dl (equivalent to > 2+ proteinuria)

3. Age less than 18 years

4. Prior therapy with formalin or carboprost 1 mg % administered intravesically

5. Hypersensitivity to cidofovir, probenecid or sulfa-containing medications

6. Have received prior cidofovir therapy within 2 weeks.

7. Prior enrollment in the study

8. Women who are pregnant or breast-feeding

9. Evidence of end-organ adenoviral infection

Roy F. Chemaly, MD, MPH, MBA, Phone: 713-792-6830

UT MD Anderson Cancer Center, Houston, Texas 77030, United States

UT MD Anderson Cancer Center

Starting date: April 2012
Last updated: November 4, 2011