Ignite Creation Date:
2024-05-05 @ 9:42 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001016
Status:
COMPLETED
Last Update Posted:
2008-09-30
First Post:
1999-11-02
Brief Title:
A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies
Status:
COMPLETED
Status Verified Date:
1993-07
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 determine the safety and effectiveness of an investigational drug trimetrexate TMTX with leucovorin rescue LCV in the treatment of Pneumocystis carinii pneumonia PCP in patients who have AIDS are HIV positive or are at high risk for HIV infection and who have demonstrated serious adverse effects from the conventional therapies for PCP
The drugs usually used to treat PCP in AIDS patients trimethoprim sulfamethoxazole and pentamidine have had to be discontinued in many patients because of severe adverse effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests In a preliminary trial TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects
The drugs usually used to treat PCP in AIDS patients trimethoprim sulfamethoxazole and pentamidine have had to be discontinued in many patients because of severe adverse effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests In a preliminary trial TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects
Detailed Description:
The drugs usually used to treat PCP in AIDS patients trimethoprim sulfamethoxazole and pentamidine have had to be discontinued in many patients because of severe adverse effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests In a preliminary trial TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects
AMENDED 080190 As of August 31 1989 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP214 in TX 301ACTG 0039 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 greater than 5 x normal in 94 patients anemia less than 79 gdl in 109 neutropenia less than 750 cellsmm3 in 58 fever greater than 40 degrees C in 37 and thrombocytopenia less than 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 counts 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 PCP214 in TX 301ACTG 0039 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 greater than 5 x normal in 94 patients anemia less than 79 gdl in 109 neutropenia less than 750 cellsmm3 in 58 fever greater than 40 degrees C in 37 and thrombocytopenia less than 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 counts 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?: