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

Primary Purpose

Hematologic Malignancies, Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ridaforolimus
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Relapsed or refractory hematologic malignancies

Eligibility Criteria

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

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

Sites / Locations

  • University of Chicago Hospitals, Section of Hematology/Oncology
  • Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place
  • The Cancer Institute of New Jersey
  • New York Presbyterian Hospital, Weill College of Cornell University
  • Morris Cancer Center - Duke University Medical Center, Adult Bone Marrow Transplant Clinic
  • Gabrail Cancer Center
  • Jeane's Hospital of TUHS
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

AP23573 12.5 mg IV as monotherapy once daily for 5 days, every 2 weeks

Outcomes

Primary Outcome Measures

To assess efficacy of AP23573 in patients with relapsed or refractory hematologic malignancies.

Secondary Outcome Measures

Evaluating time to progression, progression-free survival, duration of response and safety

Full Information

First Posted
June 24, 2004
Last Updated
August 18, 2015
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00086125
Brief Title
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

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
June 2004 (undefined)
Primary Completion Date
June 2006 (Actual)
Study Completion Date
June 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Ariad Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies, Leukemia, Myelodysplastic Syndromes, Myeloid Metaplasia, Lymphoma
Keywords
Relapsed or refractory hematologic malignancies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
AP23573 12.5 mg IV as monotherapy once daily for 5 days, every 2 weeks
Intervention Type
Drug
Intervention Name(s)
ridaforolimus
Other Intervention Name(s)
deforolimus, AP23573, MK-8669, ridaforolimus was also known as deforolimus until May 2009
Intervention Description
AP23573 12.5 mg IV as monotherapy once daily for 5 days, every 2 weeks
Primary Outcome Measure Information:
Title
To assess efficacy of AP23573 in patients with relapsed or refractory hematologic malignancies.
Time Frame
Duration of study
Secondary Outcome Measure Information:
Title
Evaluating time to progression, progression-free survival, duration of response and safety
Time Frame
Duration of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Haluska, M.D., Ph.D.
Organizational Affiliation
Ariad Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Chicago Hospitals, Section of Hematology/Oncology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
New York Presbyterian Hospital, Weill College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Morris Cancer Center - Duke University Medical Center, Adult Bone Marrow Transplant Clinic
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Jeane's Hospital of TUHS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18451242
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.
Results Reference
result

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

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