A Trial of Two Doses of 2',3'-Dideoxycytidine (ddC) in the Treatment of Children With Symptomatic HIV Infection Who Are Intolerant of AZT and/or Who Show Progressive Disease While on AZT

HIV Infections Clinical Trial

Official title:

A Trial of Two Doses of 2',3'-Dideoxycytidine (ddC) in the Treatment of Children With Symptomatic HIV Infection Who Are Intolerant of AZT and/or Who Show Progressive Disease While on AZT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000653
• Other study ID #: ACTG 138
• Secondary ID: 11113
• Status: Completed
• Phase: Phase 2
• Est. completion date: June 1995

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate and compare the long-term (48-177 weeks) safety, tolerance, and efficacy of two doses of zalcitabine ( dideoxycytidine; ddC ) taken orally every 8 hours in children with symptomatic HIV infection who have one of the following: intolerance to zidovudine ( AZT ) (development of toxicity during prolonged AZT therapy), demonstrated disease progression after 6 months of AZT therapy, OR both AZT intolerance and disease progression after 6 months of AZT therapy.

As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

Description:

As useful as AZT appears to be in the treatment of patients infected with HIV, it is associated with significant toxicity in some patients, and it does not prevent ultimate progression to AIDS and eventual mortality. Thus, there is a clear need for new antiretroviral drugs, and ddC is one such promising agent.

Patients receive oral ddC for 48 to 177 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: June 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Procrit.

• Amphotericin B (1 mg/kg up to 5 days/week).

• Prophylaxis treatment as per ACTG recommendations for Pneumocystis carinii pneumonia.

• Acyclovir (up to 1000 mg/day PO; for > 1000 mg/day PO or for any IV dose, suggest interrupting ddC).

• Ketoconazole (up to 10 mg/kg/day).

• Nystatin.

• Aspirin, acetaminophen, sedatives, and barbiturates (for up to 72 hours).

• Isoniazid (INH), if there is no evidence of peripheral neuropathy at entry. Children should receive pyridoxine, 25

• 50 mg/day to avoid possible INH-associated neuropathy.

• Trimethoprim / sulfamethoxazole (T/S).

• Immunoglobulin therapy.

• Aerosolized pentamidine.

• Drugs with little nephro-, hepato-, cytotoxicity that the patient has been taking and tolerating well for an ongoing condition.

Concurrent Treatment:

Allowed:

• Immunoglobulin therapy.

• Nutritional support (for children with wasting syndrome and/or malnutritional) including hyperalimentation (TPN) of dietary supplements.

AMENDED:

• Patients enrolled in ACTG 051 may participate in ACTG 138 if they show intolerance to AZT or show disease progression after 6 months of AZT therapy and meet entry criteria for the study.

ORIGINAL design:

• Patients enrolled in ACTG protocols 051 or 128 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this protocol.

Patients must have the following:

• Absence of acute opportunistic infection at time of entry.

• However, if patient is successfully treated for opportunistic infection and has remained stable for 2 weeks after treatment, the patient is then allowed to enter the study. Children receiving maintenance therapy for > 4 weeks are eligible.

• Parent or guardian available to give written informed consent.

Allowed at time of study entry:

• Prophylaxis treatment as per ACTG recommendations, for Pneumocystis carinii pneumonia (PCP).

• Immunoglobulin therapy.

Prior Medication:

AMENDED:

• AZT or ddI up until study entry, other antiretrovirals up until 4 weeks of study entry

Allowed:

• Zidovudine (AZT) within 4 weeks of entry.

• Dideoxyinosine (ddI) within 43 weeks of entry if no peripheral neuropathy has been observed while receiving ddI.

• Other toxicities observed while on ddI must resolve to level 2 or better before patient can begin treatment with ddC.

• Vitamin, folate, iron supplements.

Exclusion Criteria

Co-existing Condition:

AMENDED:

• 04-25-91 Additional excluded symptoms and conditions:

• Symptomatic cardiomyopathy.

• Seizures which are not well controlled by ongoing anticonvulsant therapy.

• Active malignancy requiring concomitant chemotherapy.

• Symptomatic pancreatitis.

• Grade I or greater peripheral neuropathy.

• Receiving concomitant zidovudine (AZT).

• Patients with the following conditions or symptoms are excluded:

• Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.

• Known hypersensitivity to dideoxycytidine (ddC).

Concurrent Medication:

Excluded:

• Other antiviral agents, biological modifiers, and investigational medications.

• Drugs with potential to cause peripheral neuropathy, including chloramphenicol, iodoquinol, phenytoin, ethionamide, gold, ribavirin, vincristine, cisplatin, dapsone, disulfiram, glutethimide, hydralazine, metronidazole, nitrofurantoin.

Patients with the following are excluded:

• Acute bacterial infections requiring IV or oral antibiotic treatment at time of entry.

• Known hypersensitivity to dideoxycytidine (ddC).

• Active opportunistic infection requiring treatment with an excluded concomitant medication.

Prior Medication:

Excluded:

• Antiretroviral agents (other than zidovudine (AZT) or didanosine (ddI)) within 4 weeks of entry.

• Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry.

• Any other experimental therapy, drugs that cause prolonged neutropenia, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Disease Progression
• HIV Infections
• Infections

Intervention

Drug:
• Zalcitabine

Locations

Country	Name	City	State
Puerto Rico	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.	Bayamon
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia
United States	Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases	Baltimore	Maryland
United States	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York
United States	UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases	Chapel Hill	North Carolina
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois
United States	DUMC Ped. CRS	Durham	North Carolina
United States	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey
United States	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York
United States	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Metropolitan Hosp. NICHD CRS	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	Children's National Med. Ctr., ACTU	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7. — View Citation

Spector SA, Blanchard S, Connor EM, Salgo MP, McNamara J. Results of a clinical trial comparing two doses of 2'3'-dideoxycytidine (ddC) in the treatment of children with symptomatic human immunodeficiency virus (HIV) infection who were intolerant or had failed zidovudine (ZDV) therapy (ACTG 138). The Pediatric AIDS Clinical Trials Group. American Pediatric Society 104th annual meeting and Society for Pediatric Research 63rd annual meeting; 1994 May 2-5; Seattle. Pediatr AIDS HIV Infect. 1994 Oct;5(5):323 (unnumbered abstract)