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

NCT00000989 | Completed

• 2 other identifiers: ACTG 07311047
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Cytomegalovirus Retinitis; HIV Infections

Keywords

Retinitis; Ganciclovir; Drug Evaluation; Drug Therapy, Combination; Cytomegalovirus Infections; Acquired Immunodeficiency Syndrome; Zidovudine

Interventions

Zidovudine DRUG

Sargramostim DRUG

Ganciclovir DRUG

Eligibility Criteria

• Age: 13 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Schering-Plough: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (4)

UCLA CARE Center CRS

Los Angeles, California, 90095, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, 10021, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 275997215, United States

Location

Related Publications (3)

• Hardy D, et al. Ganciclovir (GCV) and granulocyte-macrophage colony stimulating factor (GM-CSF) vs GCV alone as treatment for cytomegalovirus (CMV) retinitis (ACTG 073). Int Conf AIDS. 1992 Jul 19-24;8(1):Mo5 (abstract no MoA 0005)

  BACKGROUND

• Hardy D, Spector S, Polsky B, Crumpacker C, van der Horst C, Holland G, Freeman W, Heinemann MH, Sharuk G, Klystra J, et al. Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 2:S34-40. doi: 10.1007/BF01973600.

  PMID: 7875151 BACKGROUND

• Hardy WD. Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. J Acquir Immune Defic Syndr (1988). 1991;4 Suppl 1:S22-8.

  PMID: 1848618 BACKGROUND

MeSH Terms

Conditions

Cytomegalovirus Retinitis; HIV Infections; Retinitis; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Cytomegalovirus Infections; Acquired Immunodeficiency Syndrome

Interventions

Zidovudine; sargramostim; Ganciclovir

Condition Hierarchy (Ancestors)

Eye Infections, Viral; Eye Infections; Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Eye Diseases; Retinal Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hardy WD

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: July 1, 1992
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (4)