An Open, Prospective, Multicenter Study of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia (PCP) and Serious Intolerance to Approved Therapies

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

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, respectivel...

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• Concurrent Medication:
• Allowed:
• • Noninvestigational therapies as needed.
• • Maintenance therapy with investigational triazoles such as itraconazole and SCH 39304.
• • High-dose corticosteroids (exceed physiologic replacement doses) including oral prednisone 40 mg bid for 5 days, 40 mg daily for 5 days and then 20 mg daily for the remainder of PCP therapy. Same dose for methylprednisolone.
• Concurrent Treatment:
• Allowed:
• • Any ventilatory support, antihypertensive agents, invasive monitoring, and other necessary medical intervention, according to his/her medical status, personal wishes, and the judgment of his/her physician.
• Patients must have:
• • HIV seropositivity.
• • Diagnosis of Pneumocystis carinii pneumonia (PCP).
• * Serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX) therapy defined as follows:
• • Platelets \< 50000 platelets/mm3.
• • Neutrophil count (polys plus bands) = or \< 500 cells/mm3 on at least two occasions = or \> 12 hours apart.
• • Mucocutaneous reaction - blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus.
• • Hepatitis demonstrated by transaminase elevation \> 5 times the upper limit of normal, or = or \> 300 IU if baseline is abnormal.
• • Drug fever with daily temperature = or \> 103 degrees F beginning after the 5th day of treatment persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause.
• • Any other severe or life-threatening adverse reaction to TMP / SMX which, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable as determined on a case-by-case basis.
• * Serious intolerance to pentamidine therapy defined as follows:
• • Platelets \< 50000 platelets/mm3.
• • Neutrophil count (polys plus bands) = or \< 500 cells/mm3 on at least two occasions = or \> 12 hours apart.
• • Serum creatinine \> 3.0 mg/dl.
• • Systolic blood pressure \< 90 mm requiring supportive therapy.
• • Symptomatic hypoglycemia with blood glucose \< 40, or hyperglycemia requiring therapy.
• • Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase).
• • Any other severe or life-threatening adverse reaction to pentamidine, which, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable as determined on a case-by-case basis.
• • Informed consent by patient or legal guardian.
• Prior Medication:
• Required:
• • Trimethoprim / sulfamethoxazole and pentamidine therapies.
• Prior Medication:
• Allowed:
• • Myelosuppressive or nephrotoxic agents including zidovudine.
• • History of high-risk behavior for HIV infection - homosexual or bisexual men, intravenous drug abusers, recipients of HIV-infected blood products, or sexual partners of persons in these groups may be admitted without proof of HIV infection.
• • Exclusion Criteria
• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• • History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
• • Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.
• Concurrent Medication:
• Excluded:
• • Myelosuppressive or nephrotoxic agents including zidovudine and ganciclovir.
• • Investigational therapies.
• Patients with the following are excluded:
• • History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
• • Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.