Study of AP23573 in Patients With Relapsed or Refractory Hematologic Malignancies (8669-024)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00086125
First received: June 24, 2004
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Hematologic Malignancies
Leukemia
Myelodysplastic Syndromes
Myeloid Metaplasia
Lymphoma
Drug: ridaforolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AP23573, an mTOR Inhibitor, in Patients With Relapsed or Refractory Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • To assess efficacy of AP23573 in patients with relapsed or refractory hematologic malignancies. [ Time Frame: Duration of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluating time to progression, progression-free survival, duration of response and safety [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]

Enrollment: 57
Study Start Date: June 2004
Study Completion Date: June 2006
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AP23573 12.5 mg IV as monotherapy once daily for 5 days, every 2 weeks
Drug: ridaforolimus
AP23573 12.5 mg IV as monotherapy once daily for 5 days, every 2 weeks
Other Names:
  • deforolimus
  • AP23573
  • MK-8669
  • ridaforolimus was also known as deforolimus until May 2009

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086125

Locations
United States, Illinois
University of Chicago Hospitals, Section of Hematology/Oncology
Chicago, Illinois, United States, 60637
United States, Missouri
Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place
St. Louis, Missouri, United States, 63110
United States, New Jersey
The Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
New York Presbyterian Hospital, Weill College of Cornell University
New York, New York, United States, 10021
United States, North Carolina
Morris Cancer Center - Duke University Medical Center, Adult Bone Marrow Transplant Clinic
Durham, North Carolina, United States, 27705
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
United States, Pennsylvania
Jeane's Hospital of TUHS
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Ariad Pharmaceuticals
Investigators
Study Director: Frank Haluska, M.D., Ph.D. Ariad Pharmaceuticals
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00086125     History of Changes
Other Study ID Numbers: 8669-024, AP23573-04-201
Study First Received: June 24, 2004
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Relapsed or refractory hematologic malignancies

Additional relevant MeSH terms:
Metaplasia
Myelodysplastic Syndromes
Neoplasms
Preleukemia
Primary Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on October 22, 2014