A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000691

Collaborator

(none)

156

Enrollment

Locations

14.2

Patients Per Site

Study Details

Study Description

Brief Summary

To examine the usefulness and safety of the antiviral drug foscarnet in treating AIDS patients with cytomegalovirus (CMV) infection that is causing sight-threatening inflammation of the retina in one or both eyes (CMV retinitis). Because of the seriousness of sight-threatening CMV retinitis in AIDS patients and a lack of other available treatments for those patients who cannot be treated with ganciclovir (DHPG) (because of its toxic effect on the body's blood-forming cells, because it did not control the disease, or because patient's blood cell or platelet counts are too low to begin with), it is worthwhile to try an immediate trial with foscarnet. AMENDED: ACTG 093 was originally designed as a randomized dose-ranging study of foscarnet maintenance therapy. Patients enrolled between March 17, 1989, and January 1, 1990, received either 60 mg/kg/day or 90/mg/kg day as maintenance therapy following the 2 week induction period. Based on the preliminary results of ACTG 015/915, which studied maintenance doses of foscarnet of 60 mg/kg/day, 90 mg/kg/day and 120 mg/kg/day, the 60-mg/kg/day and 90/mg/kg/day arms of this study have been closed. All patients entering the study beginning January 2, 1990 will receive foscarnet maintenance therapy on a 120/mg/kg/day algorithm following induction.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Retinitis HIV Infections	Drug: Foscarnet sodium	Phase 2

Detailed Description

Because of the seriousness of sight-threatening CMV retinitis in AIDS patients and a lack of other available treatments for those patients who cannot be treated with ganciclovir (DHPG) (because of its toxic effect on the body's blood-forming cells, because it did not control the disease, or because patient's blood cell or platelet counts are too low to begin with), it is worthwhile to try an immediate trial with foscarnet. AMENDED: ACTG 093 was originally designed as a randomized dose-ranging study of foscarnet maintenance therapy. Patients enrolled between March 17, 1989, and January 1, 1990, received either 60 mg/kg/day or 90/mg/kg day as maintenance therapy following the 2 week induction period. Based on the preliminary results of ACTG 015/915, which studied maintenance doses of foscarnet of 60 mg/kg/day, 90 mg/kg/day and 120 mg/kg/day, the 60-mg/kg/day and 90/mg/kg/day arms of this study have been closed. All patients entering the study beginning January 2, 1990 will receive foscarnet maintenance therapy on a 120/mg/kg/day algorithm following induction.

AMENDED: The ACTG 093 optional extended maintenance therapy period will conclude on January 2, 1991 in order to facilitate timely analysis of this study. All patients who wish to continue foscarnet therapy should be referred to Astra Protocol 90-FOS-14 at telephone number 800-292-5775. Original design: Patients are placed into two groups: (1) patients who have a sight-threatening lesion in the retina of an eye with vision that can be saved (corrected vision of 20/100 or better) and who cannot be treated with DHPG, and (2) patients whose retinitis has quickly gotten worse and/or has shown resistance to DHPG treatment. Both groups will receive a beginning (induction) dose of foscarnet by vein (IV) for 2 weeks, followed by a maintenance dose for 8 weeks with an option to continue up to 24 weeks. AMENDED: Patients entering the study on or after 01/02/90 receive the standard two week course of foscarnet induction therapy and receive maintenance therapy. Treatment is given for a ten week study period or until progression occurs or toxicity endpoints are reached. If retinitis is stable and foscarnet well-tolerated, maintenance therapy may be extended for a period not to exceed 1 year.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure

Actual Study Completion Date :

Aug 1, 1992

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry.
Therapy with vancomycin.
Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry.
Initiate or resume zidovudine (AZT) in 2nd week of foscarnet maintenance therapy at dose of 100 or 200 mg q4h at investigator's discretion.
Initiate or continue erythropoietin therapy via the treatment IND mechanism.
Initiate or continue therapy with investigational triazoles for disseminated fungal infections. Caution should be used in concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient.

Prior Medication:

Allowed:

Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry.
Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

Corneal, lens, or vitreous opacification that precludes examination of the fundi.
Clinically significant pulmonary or neurologic impairment, including intubation or coma.
Karnofsky performance status = or < 50.

Concurrent Medication:

Excluded:

Immunomodulators.
Biologic response modifiers.
Investigational agents (other than erythropoietin and investigational triazoles).
Ganciclovir.
Didanosine (ddI).
Systemic acyclovir.
CMV hyperimmune serum / globulin.
Interferons.
Nephrotoxic agents including aminoglycosides, amphotericin B, parenteral pentamidine.
Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient.

Patients with the following are excluded:

Corneal, lens, or vitreous opacification that precludes examination of the fundi.
Clinically significant pulmonary or neurologic impairment, including intubation or coma.
Unwilling or unable to suspend zidovudine treatment until 2nd week of foscarnet maintenance therapy.

Prior Medication:

Excluded:

Foscarnet for cytomegalovirus retinitis.
Systemic acyclovir.
Immunomodulators.
Biologic response modifiers.
Investigational agents (other than erythropoietin and investigational triazoles).

AIDS patients with active cytomegalovirus (CMV) retinitis who cannot be treated with ganciclovir. At least one pending CMV culture from both blood (buffy-coat) and urine must be obtained prior to study entry. Patients must be able to give informed consent. Patients with a history of a seizure disorder or central nervous system mass lesion will be included.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	Ucsf Aids Crs	San Francisco	California	United States	94114
3	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
4	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
5	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
6	Washington U CRS	Saint Louis	Missouri	United States
7	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
8	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
9	Cornell University A2201	New York	New York	United States	10021
10	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
11	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710