MLN4924 for the Treatment of Acute Myelogenous Leukemia, Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia

Phase 1

Completed

• Conditions: Myelodysplastic Syndrome; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia
• Interventions: Drug: MLN4924; Drug: Azacitidine

• Registration Number: NCT00911066
• Lead Sponsor: Millennium Pharmaceuticals, Inc.

Brief Summary

An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging treatment does not exist or is no longer effective.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-05-28
• Study First Submitted QC: 2009-05-28
• Study Start: 2009-06
• Study First Posted: 2009-06-01
• Primary Completion: 2013-08
• Study Completion: 2013-10
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-03
• Last Update Posted: 2013-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• Age greater than or equal to 18 years

• Have the following diagnosis:

  • AML or ALL (for the dose escalation phase only)including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve complete response (CR) or who have relapsed after prior therapy and are not candidates for potentially curative treatment.
  • Acute Promyelocytic Leukemia (APL) patients are not eligible
  • AML or ALL patients who are over age 60 and have not received prior therapy are also eligible if they are not candidates for standard induction chemotherapy
  • High-grade MDS, defined as > 10% blasts on bone marrow examination
  • Low-grade MDS, defined as < 10% blasts on bone marrow examination (Schedule B expansion cohort only)

• Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Female patients who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse

• Male patients who agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse

• Voluntary written consent

• Suitable venous access

• Adequate clinical laboratory values during the screening period as specified in the protocol

• Patients who are on hydroxyurea may be included in the study and may continue on hydroxyurea while participating in this study.

Exclusion Criteria

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Any serious medical or psychiatric illness
• Treatment with any investigational products
• Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
• Major surgery within 14 days before the first dose of study drug
• Life-threatening illness unrelated to cancer
• Clinically uncontrolled central nervous system (CNS) involvement
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
• Evidence of uncontrolled cardiovascular conditions as specified in the protocol
• Diarrhea > Grade 1, based on the NCI CTCAE categorization
• Systemic treatment with prohibited medications
• Ongoing anticoagulant therapy (eg, aspirin, Coumadin, heparin) that cannot be held to permit bone marrow sampling
• Use of acetaminophen, acetaminophen-containing products, and statins are not permitted on the day before dosing, day of dosing, and day after dosing with MLN4924

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MLN4924	MLN4924	-
Azacitidine	Azacitidine	-

Primary Outcome Measures

Name	Time	Method
Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements	12 months

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters	12 months
Pharmacodynamic effects	12 months
Assess disease response	12 months
Heart corrected QT intervals	During screening and during Cycle 1, Days 1 and 15

Trial Locations

Locations (6)

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Johns Hopkins Kimmel Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Robert H. Lurie Comprehensive Cancer Center Northwestern University; 🇺🇸 Chicago, Illinois, United States

Institute for Drug Development; 🇺🇸 San Antonio, Texas, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States