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

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000653

Collaborator

Hoffmann-La Roche (Industry)

140

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zalcitabine	Phase 2

Detailed Description

Patients receive oral ddC for 48 to 177 weeks.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Jun 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States	90095
2	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
3	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States	92093
4	UCSF Pediatric AIDS CRS	San Francisco	California	United States	94143
5	Children's National Med. Ctr., ACTU	Washington	District of Columbia	United States	20010
6	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida	United States	33161
7	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia	United States	30303
8	Cook County Hosp.	Chicago	Illinois	United States	60612
9	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois	United States	60612
10	Chicago Children's CRS	Chicago	Illinois	United States	60614
11	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana	United States
12	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States
13	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland	United States	21201
14	Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases	Baltimore	Maryland	United States	21287
15	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts	United States	02115
16	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts	United States	02118
17	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts	United States	01199
18	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts	United States	01655
19	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey	United States
20	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York	United States	10456
21	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York	United States	11203
22	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York	United States
23	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York	United States	11042
24	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States	10016
25	Metropolitan Hosp. NICHD CRS	New York	New York	United States	10029
26	Columbia IMPAACT CRS	New York	New York	United States	10032
27	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York	United States	10037
28	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
29	UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases	Chapel Hill	North Carolina	United States	27599
30	DUMC Ped. CRS	Durham	North Carolina	United States	27710
31	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania	United States	19134
32	Texas Children's Hosp. CRS	Houston	Texas	United States	77030
33	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.	Bayamon		Puerto Rico	00619
34	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00936
35	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico