Clinical trial NCT00086125: Study of AP23573 in Patients With Relapsed or Refractory Hematologic Malignancies (8669-024)(COMPLETED)
Official title: A Phase II Study of AP23573, an mTOR Inhibitor, in Patients With Relapsed or Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Malignancies
Leukemia
Myelodysplastic Syndromes
Myeloid Metaplasia
Lymphoma
Keywords: Relapsed or refractory hematologic malignancies
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Ariad Pharmaceuticals
First posted: 2004-06-28
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this phase II study is to assess the efficacy of AP23573 in patients with specified relapsed or refractory hematological malignancies.

Detailed description: The primary objective of the trial is to assess the efficacy of AP23573 in patients with specified relapsed or refractory hematological malignancies by evaluating the response rates as defined for the individual malignancy categories. Secondary objectives include evaluating time to disease progression, progression-free survival and duration of response; evaluating the pharmacokinetic and pharmacodynamic characteristics of AP23573; describing health-related quality of life measurements; and exploring the safety and tolerability of AP23573 at the specified dose level.

Protocol Outline: Open label, non-randomized parallel cohorts of five disease-specific cohorts with a minimum of 21 patients per cohort. Each patient receives a fixed dose of AP23573 administered intravenously (IV) over 30 minutes daily for five days (QDx5) to be repeated every 2 weeks.

Eligibility criteria: Inclusion Criteria (Patients must meet each of the following criteria to be eligible for participation in the trial):

* Male or female patients ≥ 18 years of age
* Patients must have histologically-confirmed diagnoses of relapsed or refractory hematologic malignancy as specified in the protocol
* Patients must have an ECOG performance status of 0 to 2
* Patients must have adequate renal and liver function as demonstrated by laboratory values performed within 5 days, inclusive, prior to administration of the first dose of AP23573
* Patients must be able to understand and give written informed consent

Exclusion Criteria (Patients meeting any of the following criteria are ineligible for participation in the study):

* Women who are pregnant or lactating
* Patients may not have had cytotoxic chemotherapy or radiotherapy within 14 days prior to study entry
* Patients may not receive any investigational anti-cancer agent while on this study or within 14 days prior to the first dose of AP23573
* Patients with known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug formulation
* Patients with known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
* Patients with significant uncontrolled cardiovascular disease
* Patients with known HIV infection
* Patients with any uncontrolled infection
* Patients receiving immunosuppressive agents other than prescribed corticosteroids
* Patients who have had prior therapy with rapamycin, any rapamycin analog or tacrolimus
* Patients with inadequate recovery from any prior surgical procedure or patients having undergone any major surgical procedure within 14 days prior to the first dose of AP23573
* Patients with any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
* Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
* Patients with another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinomas in situ)
* Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements

Drugs and Other Treatments to be Excluded (The following drugs and other treatments are not permitted for patients enrolling in the study, either during or within two weeks prior to the first dose of AP23573, unless otherwise specified):

* Chemotherapeutic agents with the following exception that therapy with nitrosoureas (including generics) cannot be given within six weeks prior to the first dose of AP23573
* Other antineoplastic agents
* Immunotherapy (including vaccines) or biological response modifier therapy
* Systemic hormonal therapy with exceptions as specified in the protocol
* Herbal preparations or related OTC preparations containing herbal ingredients (e.g., St John's Wort)
* Radiotherapy for the primary malignancy
* Any other investigational agent during the course of the trial should be discussed with the Sponsor prior to use

Primary outcomes:
measure: To assess efficacy of AP23573 in patients with relapsed or refractory hematologic malignancies.
timeFrame: Duration of study
Secondary outcomes:
measure: Evaluating time to progression, progression-free survival, duration of response and safety
timeFrame: Duration of study
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Hospitals, Section of Hematology/Oncology
state: Illinois
city: St. Louis
country: United States
facility: Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place
state: Missouri
city: New Brunswick
country: United States
facility: The Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Hospital, Weill College of Cornell University
state: New York
city: Durham
country: United States
facility: Morris Cancer Center - Duke University Medical Center, Adult Bone Marrow Transplant Clinic
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Jeane's Hospital of TUHS
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Ariad Pharmaceuticals
name: Frank Haluska, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Rizzieri DA, Feldman E, Dipersio JF, Gabrail N, Stock W, Strair R, Rivera VM, Albitar M, Bedrosian CL, Giles FJ. A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2008 May 1;14(9):2756-62. doi: 10.1158/1078-0432.CCR-07-1372.