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A Phase 1 Dose Escalation Study of TAK-901 in Subjects With Advanced Hematologic Malignancies

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TAK-901
Sponsored by
Millennium Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, or blast crisis, Intermediate or high risk myelodysplastic syndrome, Philadelphia chromosome-negative CML (including blast phase), All subtypes of myeloid metaplasia with myelofibrosis; advanced polycythemia

Eligibility Criteria

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

Main Inclusion Criteria:

  1. The subject has one of the following confirmed diseases that is refractory to or relapsed from established therapies. Note: A subject with one of these disease who is intolerant (as defined in the protocol) to established therapies is also allowed:

    1. Acute myelogenous leukemia
    2. Acute lymphoblastic leukemia
    3. Chronic myelogenous leukemia (CML) (chronic phase, accelerated phase, or blast crisis)
    4. Chronic lymphocytic leukemia
    5. Multiple myeloma
    6. Waldenstrom's macroglobulinemia
    7. Intermediate or high risk myelodysplastic syndrome
    8. One of the following myeloproliferative disorders:

      • Philadelphia chromosome-negative CML (including blast phase).
      • All subtypes of myeloid metaplasia with myelofibrosis.
      • Advanced polycythemia vera in the spent phase (ie, presence of anemia).
    9. Non-Hodgkins lymphoma
  2. The interval between the last prior treatment and the start of study drug administration is at least 30 days for radiotherapy, at least 14 days for cytotoxic chemotherapy (42 days for nitrosureas or mitomycin C), and at least 5 half-lives for noncytotoxic agents. The only exception is hydroxyurea, which can be used prior to starting study drug and during Cycle 1, as defined in the protocol.
  3. For subjects with prior autologous bone marrow or peripheral blood stem cell transplantation, the interval between transplant and the start of study drug administration is at least 30 days.
  4. For subjects with prior allogeneic bone marrow or peripheral blood stem cell transplantation, the interval between transplant and the start of study drug administration is at least 90 days.
  5. If taking steroids chronically, the subject has been receiving a stable steroid dose for at least 21 days prior to the start of study drug administration, and the daily steroid dose does not exceed the equivalent of 20 mg prednisone.
  6. The subject is aged 18 years or older.
  7. The subject weighs at least 45 kg.
  8. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  9. The subject has adequate liver and kidney function.
  10. The subject has adequate heart function (left ventricular ejection fraction ≥ 50%).

Main Exclusion Criteria:

Any subject who meets any of the following criteria will not qualify for entry into the study:

  1. The subject has a platelet count (untransfused) < 50,000/mm3 and/or an absolute neutrophil count < 1000/mm3 that is not caused by the underlying disease infiltrating the bone marrow.
  2. The subject has evidence of active malignancy in the central nervous system (CNS)or has had CNS involvement documented within the past 90 days. Subjects who are receiving maintenance intrathecal chemotherapy for previous CNS involvement but have no current evidence of disease are allowed if the CNS involvement was documented more than 90 days ago.
  3. The subject has any evidence of acute or chronic graft versus host disease.
  4. The subject has a history of hypersensitivity or allergic reactions attributed to compounds of similar chemical composition to TAK-901 or its excipient, Captisol.
  5. The subject is pregnant or lactating.
  6. The subject has had a myocardial infarction, cerebrovascular accident, transient ischemic attack, clinically significant ventricular arrhythmia, or pulmonary embolus within 6 months prior to the start of study drug administration.
  7. The subject's electrocardiogram demonstrates an abnormal QT interval , as defined by the protocol.
  8. The subject requires dialysis.
  9. The subject is on systemic anticoagulation therapy.
  10. The subject has an uncontrolled intercurrent illness as defined in the protocol.
  11. The subject is known to have human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
  12. The subject has a currently active second malignancy other than nonmelanoma skin cancer or in situ carcinoma of the cervix. A malignancy is considered to be currently active if the subject is receiving ongoing therapy or has been in remission for less than 2 years prior to the first dose of study drug.

Sites / Locations

  • University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

TAK-901

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose(MTD)of TAK-901 in subjects with advanced hematologic malignancies.
To further assess the safety and tolerability of TAK-901 at or below the MTD in an expanded cohort of subjects in order to select a dose for future studies.

Secondary Outcome Measures

To evaluate the pharmacokinetic profile of TAK-901 and its primary metabolite (M-I).
To make a preliminary assessment of the clinical activity of TAK-901.
To make a preliminary assessment of the effects of TAK-901 on pharmacodynamic biomarkers.
To make a preliminary assessment of the association between selected genetic markers and TAK-901 response and/or pharmacokinetic parameters.

Full Information

First Posted
December 10, 2008
Last Updated
July 1, 2013
Sponsor
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00807677
Brief Title
A Phase 1 Dose Escalation Study of TAK-901 in Subjects With Advanced Hematologic Malignancies
Official Title
A Phase 1 Dose Escalation Study of TAK-901 in Subjects With Advanced Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of TAK-901 in subjects with advanced hematological malignancies, and to further assess the safety and tolerability of TAK-901 at or below the MTD in an expanded cohort of subjects in order to select a dose for future studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukemia, Multiple Myeloma, Waldenstrom's Macroglobulinemia, Myelodysplastic Syndrome, Philadelphia Chromosome-negative CML, Myeloid Metaplasia, Myelofibrosis, Advanced Polycythemia, Non-Hodgkins Lymphoma
Keywords
Chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, or blast crisis, Intermediate or high risk myelodysplastic syndrome, Philadelphia chromosome-negative CML (including blast phase), All subtypes of myeloid metaplasia with myelofibrosis; advanced polycythemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
TAK-901
Intervention Type
Drug
Intervention Name(s)
TAK-901
Intervention Description
TAK-901 will be administered via IV infusion over a 3-hour period on Days 1,4,8,11,15,18,22, and 25 of each 28-day cycle.
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose(MTD)of TAK-901 in subjects with advanced hematologic malignancies.
Time Frame
Duration of the study
Title
To further assess the safety and tolerability of TAK-901 at or below the MTD in an expanded cohort of subjects in order to select a dose for future studies.
Time Frame
Duration of study
Secondary Outcome Measure Information:
Title
To evaluate the pharmacokinetic profile of TAK-901 and its primary metabolite (M-I).
Time Frame
Duration of the study
Title
To make a preliminary assessment of the clinical activity of TAK-901.
Time Frame
Duration of therapy
Title
To make a preliminary assessment of the effects of TAK-901 on pharmacodynamic biomarkers.
Time Frame
Duration of therapy
Title
To make a preliminary assessment of the association between selected genetic markers and TAK-901 response and/or pharmacokinetic parameters.
Time Frame
Duration of therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: The subject has one of the following confirmed diseases that is refractory to or relapsed from established therapies. Note: A subject with one of these disease who is intolerant (as defined in the protocol) to established therapies is also allowed: Acute myelogenous leukemia Acute lymphoblastic leukemia Chronic myelogenous leukemia (CML) (chronic phase, accelerated phase, or blast crisis) Chronic lymphocytic leukemia Multiple myeloma Waldenstrom's macroglobulinemia Intermediate or high risk myelodysplastic syndrome One of the following myeloproliferative disorders: Philadelphia chromosome-negative CML (including blast phase). All subtypes of myeloid metaplasia with myelofibrosis. Advanced polycythemia vera in the spent phase (ie, presence of anemia). Non-Hodgkins lymphoma The interval between the last prior treatment and the start of study drug administration is at least 30 days for radiotherapy, at least 14 days for cytotoxic chemotherapy (42 days for nitrosureas or mitomycin C), and at least 5 half-lives for noncytotoxic agents. The only exception is hydroxyurea, which can be used prior to starting study drug and during Cycle 1, as defined in the protocol. For subjects with prior autologous bone marrow or peripheral blood stem cell transplantation, the interval between transplant and the start of study drug administration is at least 30 days. For subjects with prior allogeneic bone marrow or peripheral blood stem cell transplantation, the interval between transplant and the start of study drug administration is at least 90 days. If taking steroids chronically, the subject has been receiving a stable steroid dose for at least 21 days prior to the start of study drug administration, and the daily steroid dose does not exceed the equivalent of 20 mg prednisone. The subject is aged 18 years or older. The subject weighs at least 45 kg. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. The subject has adequate liver and kidney function. The subject has adequate heart function (left ventricular ejection fraction ≥ 50%). Main Exclusion Criteria: Any subject who meets any of the following criteria will not qualify for entry into the study: The subject has a platelet count (untransfused) < 50,000/mm3 and/or an absolute neutrophil count < 1000/mm3 that is not caused by the underlying disease infiltrating the bone marrow. The subject has evidence of active malignancy in the central nervous system (CNS)or has had CNS involvement documented within the past 90 days. Subjects who are receiving maintenance intrathecal chemotherapy for previous CNS involvement but have no current evidence of disease are allowed if the CNS involvement was documented more than 90 days ago. The subject has any evidence of acute or chronic graft versus host disease. The subject has a history of hypersensitivity or allergic reactions attributed to compounds of similar chemical composition to TAK-901 or its excipient, Captisol. The subject is pregnant or lactating. The subject has had a myocardial infarction, cerebrovascular accident, transient ischemic attack, clinically significant ventricular arrhythmia, or pulmonary embolus within 6 months prior to the start of study drug administration. The subject's electrocardiogram demonstrates an abnormal QT interval , as defined by the protocol. The subject requires dialysis. The subject is on systemic anticoagulation therapy. The subject has an uncontrolled intercurrent illness as defined in the protocol. The subject is known to have human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. The subject has a currently active second malignancy other than nonmelanoma skin cancer or in situ carcinoma of the cervix. A malignancy is considered to be currently active if the subject is receiving ongoing therapy or has been in remission for less than 2 years prior to the first dose of study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

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A Phase 1 Dose Escalation Study of TAK-901 in Subjects With Advanced Hematologic Malignancies

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