A Study of Pevonedistat in Combination With Azacitidine in Participants With Higher-risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myelogenous Leukemia (AML) With Severe Renal Impairment or Mild Hepatic Impairment

ID#: NCT03814005

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1

Recruitment Status: Recruiting

Start Date: July 10, 2019

End Date: April 06, 2021

Contact Information:
Takeda Study Registration Call Center
Summary: The purpose of this study is to characterize the pharmacokinetic (PK) of pevonedistat in participants with severe renal impairment and mild hepatic impairment.

Inclusion Criteria:

1. Has morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cell [WBC] <13,000 /mcL]. French-American-British (FAB) Classifications:

- Refractory anemia with excess blasts (RAEB), defined as having 5% to 20% myeloblasts in the bone marrow.

- CMML with 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood. OR world health organization (WHO) Classifications:

- RAEB-1, defined as having 5% to 9% myeloblasts in the bone marrow.

- RAEB-2, defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.

- CMML-2, defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.

- CMML-1 (although CMML-1 is defined as having <10% myeloblasts in the bone marrow and/or <5% blasts in the blood, these patients may enroll only if bone marrow blasts >=5%).

2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):

- Very high (>6 points).

- High (>4.5-6 points).

- Intermediate (>3-4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.

3. Has WHO-defined AML, including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, have failed to achieve CR or have relapsed after prior therapy and are not candidates for potentially curative treatment.

4. Has relapsed or refractory MDS, have previously been treated with an hypomethylating agent.

5. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.

6. Has recovered (that is, Grade <=1 toxicity) from the reversible effects of prior anticancer therapy.

7. Laboratory value requirements per study arms are:

- Estimated glomerular filtration rate (eGFR) (milliliter per minute per 1.73 square meter [mL/min/1.73^m]) >=90 (Control arm), <30 (Renal arm) and >=60 (Hepatic arm).

- Total Bilirubin <= upper limit of normal (ULN) (Control arm), <= ULN (Renal arm) and ULN
- Alanine aminotransferase (ALT) <= ULN (Control arm), <=2.5 * ULN (Renal arm) and Any (Hepatic arm).

Exclusion Criteria:

1. Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.

2. Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.

3. Known hepatic cirrhosis or severe pre-existing hepatic impairment.