Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000724
Status:
COMPLETED
Last Update Posted:
2012-12-19
First Post:
1999-11-02
Brief Title:
A Study of Trimetrexate With Leucovorin Rescue for AIDS Patients Who Are Refractory to Standard Therapies for Pneumocystis Carinii Pneumonia
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Study of Trimetrexate With Leucovorin Rescue for AIDS Patients Who Are Refractory to Standard Therapies for Pneumocystis Carinii Pneumonia
Status:
COMPLETED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To study the safety and effectiveness of trimetrexate TMTX plus leucovorin calcium rescue LCV in the treatment of Pneumocystis carinii pneumonia PCP in patients who have AIDS patients who are HIV positive or those for whom laboratory confirmation of HIV infection has not yet been established if they are at high risk for HIV infection and who have not responded to standard treatments or who have demonstrated severe or life-threatening intolerance to both conventional therapies for PCP
The drugs trimethoprim sulfamethoxazole TMP SMX and pentamidine usually used to treat PCP in AIDS patients have proven ineffective in many patients and have had to be discontinued in many other patients because of severe side effects TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests and in a preliminary trial in combination with LCV there was a high response rate without severe toxicity
The drugs trimethoprim sulfamethoxazole TMP SMX and pentamidine usually used to treat PCP in AIDS patients have proven ineffective in many patients and have had to be discontinued in many other patients because of severe side effects TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests and in a preliminary trial in combination with LCV there was a high response rate without severe toxicity
Detailed Description:
The drugs trimethoprim sulfamethoxazole TMP SMX and pentamidine usually used to treat PCP in AIDS patients have proven ineffective in many patients and have had to be discontinued in many other patients because of severe side effects TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests and in a preliminary trial in combination with LCV there was a high response rate without severe toxicity
AMENDED 080190 As of August 31 1989 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP 214 in TX 301ACTG 039 trimetrexate for patients intolerant of approved therapies and 223 in NS 401 trimetrexate for patients refractory to approved therapies The analysis of overall response rate stringently defined as having received at least 14 days of trimetrexate and being alive at follow-up 1 month after the completion of therapy reveals 84159 intolerant patients and 48160 refractory patients had responded for rates of 53 percent and 30 percent respectively These response rates include all individuals who received at least one dose of trimetrexate Of the 111 patients who were ventilator-dependent at study entry 18 completed a course of therapy and were alive a month later for a response rate of 16 percent All other ventilated patients died The most common severe grades 3 and 4 toxicities were transaminase elevation 5 x normal in 94 patients anemia 79 gdl in 109 neutropenia 750 cellsmm3 in 58 fever 40 C in 37 and thrombocytopenia 50000 plateletsmm3 in 27
Toxicity required discontinuation of therapy in approximately 5 percent of all patients Original design Patients entered in the study are given TMTX once a day for 21 days and LCV 4 times a day every 6 hours for 24 days Doses are determined by body size Both drugs are given by intravenous infusion but LCV may be given orally after the first 10 days Doses are adjusted if side effects such as low white blood cell count are too severe During the 21-day trial zidovudine AZT may not be used because of possible increased bone marrow toxicity AZT may be resumed as soon as the administration of TMTX and LCV has been completed After treatment with TMTX the patient may be treated with other drugs to prevent the recurrence of PCP at the discretion of hisher physician
AMENDED 080190 As of August 31 1989 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP 214 in TX 301ACTG 039 trimetrexate for patients intolerant of approved therapies and 223 in NS 401 trimetrexate for patients refractory to approved therapies The analysis of overall response rate stringently defined as having received at least 14 days of trimetrexate and being alive at follow-up 1 month after the completion of therapy reveals 84159 intolerant patients and 48160 refractory patients had responded for rates of 53 percent and 30 percent respectively These response rates include all individuals who received at least one dose of trimetrexate Of the 111 patients who were ventilator-dependent at study entry 18 completed a course of therapy and were alive a month later for a response rate of 16 percent All other ventilated patients died The most common severe grades 3 and 4 toxicities were transaminase elevation 5 x normal in 94 patients anemia 79 gdl in 109 neutropenia 750 cellsmm3 in 58 fever 40 C in 37 and thrombocytopenia 50000 plateletsmm3 in 27
Toxicity required discontinuation of therapy in approximately 5 percent of all patients Original design Patients entered in the study are given TMTX once a day for 21 days and LCV 4 times a day every 6 hours for 24 days Doses are determined by body size Both drugs are given by intravenous infusion but LCV may be given orally after the first 10 days Doses are adjusted if side effects such as low white blood cell count are too severe During the 21-day trial zidovudine AZT may not be used because of possible increased bone marrow toxicity AZT may be resumed as soon as the administration of TMTX and LCV has been completed After treatment with TMTX the patient may be treated with other drugs to prevent the recurrence of PCP at the discretion of hisher physician
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: