The Safety and Effectiveness of Ganciclovir Used Alone or in Combination With Granulocyte-Macrophage Colony Stimulating Factor in the Treatment of Cytomegalovirus (CMV) of the Eye in Patients With AIDS

• Status: Completed
• Trial end date: 1992-07-01
• Target enrollment: 0
• Participant gender: All

Summary

AMENDED: To evaluate the effect of sargramostim ( GM-CSF ) on modulating the granulocytopenia associated with concomitant DHPG and AZT therapy ( Phase B ), in terms of time to development of granulocytopenia as defined by an absolute neutrophil count ( ANC ) less than or equal to 750 cells/mm3.

Original design: To determine if granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is helpful in preventing the decreased numbers of white blood cells (infection-fighting cells) associated with ganciclovir ( DHPG ) therapy and to determine if GM-CSF can be safely used in AIDS patients with cytomegalovirus ( CMV ) retinitis.

AMENDED: In ACTG 004, among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy (5 mg/kg, 5x/week) with stable white blood cells (WBC)/absolute neutrophil counts (ANC) 7 (64 percent) required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT (600 mg/day) was added. A mean nadir ANC of 717 cells/ml was reached at a mean of 5 weeks of concomitant DHPG/AZT therapy in these patients. While recovery of depressed ANC occurred following discontinuation of study medications, progressive CMV infection (most commonly retinitis) occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption. Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPG/AZT. Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions. The study investigators concluded that the main, treatment limiting toxicity of combination DHPG/AZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia. In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy, extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol. Original design: CMV infection causes inflammation of the retina and can lead to permanent blindness. Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease. During DHPG treatment, however, about 30 to 55 percent of patients develop decreased white blood cell counts. GM-CSF, a naturally occurring human hormone, stimulates the body's bone marrow to produce more white blood cells. Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Hoffmann-La Roche; Schering-Plough
• Treatments: Ganciclovir; Ganciclovir triphosphate; Sargramostim; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Maintenance therapy for stable opportunistic infection which is not myelosuppressive.

• Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia.

• Acyclovir or other appropriate medications for appearance of Herpes simplex virus or Varicella zoster virus infections (after enrollment in study) that require systemic therapy.

• Medications absolutely necessary for the patient's welfare, at discretion of investigator.

Patients must:

• Have a diagnosis of sight-threatening cytomegalovirus (CMV) retinitis and AIDS.

• Have at least one pending culture for cytomegalovirus (CMV) from buffy coat and/or urine prior to study entry or previously documented CMV viremia or viruria within 6 weeks prior to study entry.

• Be capable of giving informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Corneal, lenticular, or vitreal opacification that precludes examination of the fundi, or evidence of other retinopathy other than cotton wool spots.

Concurrent Medication:

Excluded:

• Systemic antiviral therapy except Zidovudine (AZT) which will be added during the extended maintenance phase of the study.

• Foscarnet.

• Treatment for an active AIDS-defining opportunistic infection.

• Any potentially cytotoxic chemotherapeutic agent.

Patients with the following are excluded:

• Corneal, lenticular, or vitreal opacification that precludes examination of the fundi, or evidence of other retinopathy other than cotton wool spots.

Prior Medication:

Excluded within 14 days of study entry:

• Other immunomodulators, biologic response modifiers, or investigational agents.

• Protocol drugs.

• Foscarnet.

• Any potentially cytotoxic chemotherapeutic agent.

Prior Treatment:

Excluded within 14 days of study entry:

• Administration of cytomegalovirus hyperimmune globulin in therapeutic doses.