Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000714
Status:
COMPLETED
Last Update Posted:
2021-10-29
First Post:
1999-11-02
Brief Title:
An Open Prospective Multicenter Study of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia PCP 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:
An Open Prospective Multicenter Study of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia PCP and Serious Intolerance to Approved Therapies
Status:
COMPLETED
Status Verified Date:
2021-10
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 therapy trimetrexate plus leucovorin calcium TMTX 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 suffered severe or life-threatening ill effects from both conventional therapies for PCP 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 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 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 side effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests Also TMTX in combination with LCV had a high response rate and did not cause severe toxicity in a preliminary trial
Original design 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 side effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests Also TMTX in combination with LCV had a high response rate and did not cause severe toxicity in a preliminary trial
Detailed Description:
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 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 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 side effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests Also TMTX in combination with LCV had a high response rate and did not cause severe toxicity in a preliminary trial
Patients entered in the study are given TMTX for 21 days and LCV 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 It is essential to ensure that patients receive each and every dose of LCV and that LCV therapy is continued for a full 3 days after TMTX therapy has been completed or discontinued 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
Original design 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 side effects Currently there are no proven alternatives to these drugs TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests Also TMTX in combination with LCV had a high response rate and did not cause severe toxicity in a preliminary trial
Patients entered in the study are given TMTX for 21 days and LCV 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 It is essential to ensure that patients receive each and every dose of LCV and that LCV therapy is continued for a full 3 days after TMTX therapy has been completed or discontinued 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
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?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 11744 | REGISTRY | DAIDS ES Registry Number | None |