Clinical trial NCT00000653: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Zalcitabine
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Hoffmann-La Roche
First posted: 2001-08-31
Enrollment: 140
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

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