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
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Zalcitabine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Hoffmann-La Roche Official(s) and/or principal investigator(s):
Spector SA, Study Chair
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.
Clinical Details
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 design: Treatment
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
Minimum age: 3 Months.
Maximum age: 18 Years.
Gender(s): Both.
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.
Locations and Contacts
UPR Children's Hosp / San Juan City Hosp, San Juan 00936, Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00619, Puerto Rico
UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States
Stanford Univ School of Medicine / Pediatrics, Stanford, California 943054149, United States
Children's Hosp of Oakland, Oakland, California 946091809, United States
Kaiser Permanente / UCLA Med Ctr, Downey, California 902422814, United States
UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States
Cedars Sinai / UCLA Med Ctr, Los Angeles, California 900481804, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Northern California Pediatric AIDS Treatment Ctr / UCSF, San Francisco, California 94143, United States
Univ of Connecticut Health Ctr / Pediatrics, Farmington, Connecticut 06032, United States
Children's Hosp of Washington DC / Children's Natl Med Ctr, Washington, District of Columbia 20010, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Emory Univ School of Medicine, Atlanta, Georgia 30303, United States
Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Illinois College of Medicine, Chicago, Illinois 60612, United States
Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States
Johns Hopkins Hosp - Pediatric, Baltimore, Maryland 212874933, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Westchester Hosp, Valhalla, New York 10595, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Mount Sinai Med Ctr / Pediatrics, New York, New York 10029, United States
Metropolitan Hosp Ctr, New York, New York 10029, United States
Lincoln Hosp Ctr / Pediatrics, Bronx, New York 10451, United States
SUNY / Health Sciences Ctr at Brooklyn / Pediatrics, Brooklyn, New York 11203, United States
Northshore Hosp / Cornell Univ, Manhasset, New York 11030, United States
Schneider Children's Hosp / Long Island Jewish Med Ctr, New Hyde Park, New York 11042, United States
Bronx Lebanon Hosp Ctr, Bronx, New York 10456, United States
Beth Israel Med Ctr / Pediatrics, New York, New York 10003, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States
Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States
Additional Information
Click here for more information about Zalcitabine
Related publications: Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8. 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)
Last updated: June 23, 2005
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