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A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies

Primary Purpose

Pneumonia, Pneumocystis Carinii, HIV Infections

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Trimetrexate glucuronate
Leucovorin calcium
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia, Pneumocystis Carinii focused on measuring Trimetrexate, Pneumonia, Pneumocystis carinii, Quinazolines, Infusions, Intravenous, Injections, Intravenous, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Administration, Oral, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Blood pressure medication. Concurrent Treatment: Allowed: Blood products. Ventilatory support. Patients must have the following: Diagnosis of Pneumocystis carinii pneumonia (PCP). Be HIV positive by ELISA, HIV culture, or p24 antigenemia; or be a member of an identified risk group. Intolerant to trimethoprim / sulfamethoxazole (TMP / SMX). Intolerant to pentamidine. Prior Medication: Allowed: Trimethoprim / sulfamethoxazole trials. Pentamidine trials. Myelosuppressive agents. Nephrotoxic agents. Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients who do not meet the inclusion criteria are excluded. Concurrent Medication: Excluded: Myelosuppressive agents. Nephrotoxic agents. Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses). Patients who do not meet the inclusion criteria are excluded.

Sites / Locations

  • Warner-Lambert Parke-Davis

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
September 26, 2008
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001016
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 1993
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.
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: 08/01/90. As of August 31, 1989, 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP:214 in TX 301/ACTG 0=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 84/159 intolerant patients and 48/160 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 7.9 g/dl) in 109, neutropenia (less than 750 cells/mm3) in 58, fever (greater than 40 degrees C) in 37, and thrombocytopenia (less than 50,000 platelets/mm3) 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 his/her physician.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Pneumocystis Carinii, HIV Infections
Keywords
Trimetrexate, Pneumonia, Pneumocystis carinii, Quinazolines, Infusions, Intravenous, Injections, Intravenous, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Administration, Oral, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
None (Open Label)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Trimetrexate glucuronate
Intervention Type
Drug
Intervention Name(s)
Leucovorin calcium

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Blood pressure medication. Concurrent Treatment: Allowed: Blood products. Ventilatory support. Patients must have the following: Diagnosis of Pneumocystis carinii pneumonia (PCP). Be HIV positive by ELISA, HIV culture, or p24 antigenemia; or be a member of an identified risk group. Intolerant to trimethoprim / sulfamethoxazole (TMP / SMX). Intolerant to pentamidine. Prior Medication: Allowed: Trimethoprim / sulfamethoxazole trials. Pentamidine trials. Myelosuppressive agents. Nephrotoxic agents. Zidovudine (AZT). Exclusion Criteria Co-existing Condition: Patients who do not meet the inclusion criteria are excluded. Concurrent Medication: Excluded: Myelosuppressive agents. Nephrotoxic agents. Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses). Patients who do not meet the inclusion criteria are excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Feinberg J
Official's Role
Study Chair
Facility Information:
Facility Name
Warner-Lambert Parke-Davis
City
Morris Plains
State/Province
New Jersey
ZIP/Postal Code
07950
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies

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