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

Millennium Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Acute Myelogenous Leukemia

Acute Lymphoblastic Leukemia

Myelodysplastic Syndrome

Treatments

Drug: Azacitidine

Drug: MLN4924

Study type

Interventional

Funder types

Industry

Identifiers

NCT00911066

C15003

Details and patient eligibility

About

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.

Enrollment

72 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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