The Adult Clinical AIDS Program in the National Cancer Institute is presently recruiting for the following clinical trials for HIV infection and Kaposi's sarcoma (KS). Dr. Robert Yarchoan is the Principal Investigator for these trials:
Protocols for the treatment of HIV infection:
bis-POM-PMEA & AZT (95-C-0083)
bis-POM PMEA (adefovir dipivoxil) is a new experimental oral anti-HIV agent developed by Gilead Sciences that is being tested for safety and tolerance in combination with zidovudine (AZT). bis-POM PMEA is converted in the body to PMEA, a nucleotide analogue with potent activity in the test tube against a variety of viruses including HIV-1, HIV-2, CMV and other herpes viruses. PMEA is somewhat different from other nucleoside analogues used against HIV in that (1) the sugar ring is acyclic and (2) it already has one phosphate group. Because of the latter characteristic, the drug may be more easily phosphorylated in cells than such drugs as AZT. Also, PMEA and its structural analogue PMPA, have been shown to prevent de novo infection of SIV in macaques. A phase I/II clinical trial has shown that bis-POM PMEA has anti-HIV activity in HIV-infected patients. The current study will involve administration of a combination of AZT and 125 mg/kg/day or 250 mg/kg/day of bis-POM PMEA in symptomatic HIV-infected patients. Patients must be on AZT 500 mg/day (but no other anti-HIV drugs), have a CD4 count of 100-400, and not have current opportunistic infections. Patients will take bis-POM PMEA by mouth once daily along with oral AZT for 12 weeks. If a patient has no serious side effects during this 12 week period, he or she may be offered the option of receiving 125 mg/day of bis-POM PMEA for an additional 6 months. (This trial will be conducted at the NIH Clinical Center in Bethesda, MD. Most travel costs and a housing stipend will be provided to patients while on the protocol. However, patients will have to pay for their initial trip to the Clinical Center.) For more information, please call Tino Merced-Galindez R.N. at (800) 772-5464 ext. 562, or Dr. Lauri Welles at (301) 402-3630.
KNI-272 (Protease Inhibitor) (94-C-0040)
A Phase I study of KNI-272, an inhibitor of the HIV protease, has been initiated in the NCI. To be eligible, patients must have symptomatic HIV infection or AIDS, and must have CD4 counts of 100-400 cells/mm3. Patients must be free of active opportunistic infections at the time of entry. Patients will take KNI-272 orally as an outpatient for up to 12 weeks. An assessment will be made of the tolerance and toxicity profile, and preliminary evidence will be gathered for the potential anti-HIV activity of KNI-272. Patients may be asked to have frequent blood sampling during one or more days that they take the drug. It should be stressed that this is an experimental agent and that there is little information available on its toxicity or activity in humans. (This trial will be conducted at the NIH Clinical Center in Bethesda, MD. Most travel costs and a housing stipend will be provided to patients while on the protocol. However, patients will have to pay for their initial trip to the Clinical Center.) For more information, please call Kathy Wyvill R.N. or Jill Lietzau R.N. at (800) 772-5464 ext. 507, or Dr.Rachel Humphrey at (301) 402-3630.
SYNTHETIC HIV PEPTIDE VACCINES (Treatment protocol) (94-C-0159)
We are conducting a study to evaluate the safety of two peptide vaccines (given alone or in combination) in patients with early HIV infection. Patients entered onto the study must have >500 CD4 cells/mm3 and have preserved cardiac, hepatic, renal, and bone marrow function. Patients must be off all anti-retroviral therapy for at least 6 months and may not have received any experimental HIV vaccines. The vaccines being tested in this trial are comprised of short peptide segments of the HIV envelope, including the V3 loop. In animal studies, the peptides were able to induce neutralizing antibodies as well as cytotoxic T responses to HIV. This will be the first trial in which they are given to humans. The study will last for approximately one year, during which time the volunteers will receive 6 peptide vaccines under the skin. For more information, please call Tino Merced-Galindez R.N. at (800) 772-5464 ext. 562 or Dr. Rachel Humphrey at (301) 402-3630.
Beta-fluoro-ddA (Nucleoside analogue) (95-C-0192)
A phase I dose-escalating trial of a new nucleoside analogue, F-ddA, has been initiated in the NCI. F-ddA is an oral drug which is a fluorinated analogue of ddI (didanosine). Its activity in the test tube is similar to that of ddI but, because of the fluorine substitution , F-ddA is expected to be absorbed better than ddI. F-ddA thus does not have to be administered with buffers. Also, F-ddA does not appear to have cross-reactive resistance with ddI and is even active against strains of HIV that have multi-dideoxynucleoside resistance associated with a mutation at codon of 151 of reverse transcriptase. It is possible that F-ddA will be found to have a different toxicity profile than ddI. The aims of this trial are to study the toxicity, pharmacokinetics, virologic, immunologic and short-term activity of F-ddA. The study duration is four weeks. It is possible that it will later be extended up to 12-16 weeks when appropriate animal toxicity studies are completed. Patients will be hospitalized for the first three days, with the rest of the study performed on an outpatient basis. Weekly evaluations will be performed at the NIH Clinical Center. Patients must have documented HIV infection with CD4 counts 100-400 cells/mm3 and be off antiretroviral therapy for three weeks prior to beginning the study. More information will be available soon. (This trial will be conducted at the NIH Clinical Center in Bethesda, MD. Most travel costs and a housing stipend will be provided to patients while on the protocol. However, patients will have to pay for their initial trip to the Clinical Center.) Contact Jill Lietzau, R.N. at (800) 772-5464 ext. 508 or Dr. Lauri Welles at (301) 402-3630.
Protocols for the treatment of Kaposi's sarcoma:
TNP-470 (Anti-angiogenesis agent) (92-C-0228)
TNP-470 is an analogue of the fungal product fumagillin that has been shown to be a potent inhibitor of angiogenesis in the test tube and in animal models. It is different from most cytotoxic anticancer drugs in that it has caused little or no bone-marrow toxicity or immunosuppression in test animals. There is little experience with this drug in humans. The major toxicity in animals (seen when it was given as a bolus) has been bleeding. We are recruiting patients for a Phase I trial with this agent in patients with HIV-associated Kaposi sarcoma. Patients will receive TNP-470 every other day for 4-6 weeks. If the drug is well tolerated, patients will have the option to receive additional drug for up to a total of 18 weeks of treatment. Because the drug is given by vein every other day, patients must remain in the Maryland/DC area for the entire treatment or live in this area. The toxicity, pharmacokinetics and activity of TNP -470 will be studied. Different patients will receive increasing doses of TNP-470 until the maximum tolerated dose is identified. Patients must be on a stable dose of antiretroviral therapy or be off antiretroviral therapy, for two weeks before starting TNP-470. Patients are required to be off chemotherapy, radiation, intralesional therapy and interferon for three weeks before starting the trial. (This trial will be conducted at the NIH Clinical Center in Bethesda, MD. Most travel costs and a housing stipend will be provided to patients while on the protocol. However, patients will have to pay for their initial trip to the Clinical Center.) For more information , please contact Kathy Wyvill or Jill Lietzau at (800) 772-5464 (ext. 507) or Dr. James Pluda or (301) 496-1196.
Oral thalidomide (Anti-angiogenesis agent) (96-C-0004)
Thalidomide is a potent inhibitor of angiogenesis in animal models. This is a phase II/III trial to investigate whether oral thalidomide will be effective in the treatment of HIV-associated Kaposi's sarcoma (KS). Patients will receive the drug (at doses of up to 1000 mg/day if tolerated) for six months. The treatment period may be extended to one year in patients who appear to derive benefit against their KS. There is evidence that thalidomide has other activity in HIV-infected patients: there is evidence that it may be useful for the treatment of HIV-associated wasting syndrome (due to thalidomide-mediated inhibition of TNF-alpha) and it has activity in the therapy of HIV-related aphthous stomatitis. Thalidomide appears to have immunomodulatory (but not immunosuppressive) effects and has been shown to inhibit HIV replication in vitro. In order to enroll in the study, patients must be off anti-KS therapy for 4 weeks and be on a stable antiretroviral regimen (or be off antiretroviral therapy) for a minimum of two weeks prior to beginning the trial. Women of child-bearing age are not excluded, but are required to have a negative pregnancy test and agree to use both barrier (condom) and hormonal methods of contraception during the study. Note that pregnancy testing will be performed frequently in this group of patients. (This trial will be conducted at the NIH Clinical Center in Bethesda, MD. Most travel costs and a housing stipend will be provided to patients while on the protocol. However, patients will have to pay for their initial trip to the Clinical Center.) For more information, contact Kathy Wyvill, R.N. at (800) 772-5464 ext. 506, Tino Merced-Galindez, R.N. at (800) 772-5464 ext. 562 or Dr. Lauri Welles at (301) 402-3630.
All these trials are open to persons 18 years or older without regard to their sex, race, ethnic origin, or religion. These are experimental therapies in which the risks are not known. The decision to enter a study should be made between the patient and his or her referring physician, and patients should make sure to read and understand the informed consent before volunteering. Questions may be answered by the contact persons listed or by the Principal Investigator, Dr. Robert Yarchoan, (301) 496-0328.
Note: This statement was approved for posting by the NCI IRB.
This document was provided by Robert Yarchoan, M.D.
Chief, Retroviral Diseases Section, MB, DCS
NCI Phone: (301) 496-0328
FAX: (301) 402-3645
US Mail address: Bldg 10, Rm. 12N226, NIH, Bethesda MD 20892-1906