A Study of DSP-2033 (Alvocidib) in Patients With Acute Myeloid Leukemia

NCT03563560 | Completed Phase 1

• 1 other identifier: DC850101
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 11

Brief Summary

This is an open label, multi-center, phase 1 study of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) or cytarabine/daunorubicin (A+7+3 regimen) in patients with acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Keywords

Newly diagnosed AML; Relapsed/refractory AML; Alvocidib

Outcome Measures

Primary Outcomes (1)

• To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0

  Safety and tolerability of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) in Japanese patients with relapsed or refractory AML and in combination with cytarabine/daunorubicin (A+7+3 regimen) in Japanese newly diagnosed AML patients. Safety and tolerability analyses:The number of subjects with treatment-related adverse events as assessed by CTCAE v4.0. The number of subjects with DLT and incidence rate during the DLT evaluation period.

  2 months

Secondary Outcomes (5)

• To evaluate peak plasma concentration (Cmax) of ACM regimen and A+7+3 regimen in Japanese

  14 days

• To evaluate Area under the plasma concentration versus time curve (AUC) of ACM regimen and A+7+3 regimen in Japanese

  14 days

• To evaluate the Anti-tumor effects based on bone-marrow blasts

  2 months

• Event-free survival (EFS) (ACM regimen part only)

  12 months

• Overall survival (OS) (ACM regimen part only)

  12 months

Study Arms (2)

ACM regimen

EXPERIMENTAL

ACM regimen is for Japanese patients with relapsed or refractory AML.

Drug: Alvocidib; Drug: Cytarabine; Drug: Mitoxantrone

A+7+3 regimen

EXPERIMENTAL

A+7+3 regimen is for Japanese newly diagnosed AML patients.

Drug: Alvocidib; Drug: Cytarabine; Drug: Daunorubicine

Interventions

Alvocidib DRUG

ACM regimen:30 mg/60 mg, 30-minute intravenous (IV) infusion, followed 4-hour IV infusion from Day 1 to Day 3 A+7+3 regimen: recommended dose (RD), 30-minute IV infusion, followed 4-hour IV infusion from Day 1 to Day 3

Also known as: DSP-2033

A+7+3 regimen; ACM regimen

Cytarabine DRUG

300 or 667 mg/m2/day, 72-hour continuous IV infusion starting on Day 6 (ACM regimen)

Also known as: DSP-AraC

ACM regimen

Mitoxantrone DRUG

14 or 40 mg/m2/day, IV infusion over 1 hour to 2 hours at 12 hours after the end of DSP-AraC administration (acceptable range + 3 hours)

Also known as: DSP-MIT

ACM regimen

Daunorubicine DRUG

60 mg/m2/day, 30-minute IV infusion for 3 days from Day 5 to Day 7

Also known as: DSP-DNR

A+7+3 regimen

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \[For all parts\]
• Japanese patients diagnosed with AML by the 4th edition of WHO criteria.
• Patients aged between 20 and 64 at acquisition of informed consent.
• Have received an adequate explanation of the objectives/contents of the clinical study, anticipated therapeutic effects/pharmacology, and risks to his/her understanding, and voluntarily provide written informed consent to participation in the clinical study.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 at entry.
• Have a left ventricular ejection fraction (LVEF) ≥ 50% determined by echocardiography or multigated acquisition (MUGA) scan within 14 days prior to entry.
• Have an arterial oxygen saturation (SpO2) ≥ 90% within 14 days prior to entry.
• The laboratory test within 14 days prior to entry (for multiple tests, the most recent before the entry) meet the following criteria for major organ function.
• Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) of the institutional reference standard
• AST and ALT ≤ 2 x ULN of the institutional reference standard
• Total bilirubin ≤ 2.0 mg/dL
• Female patients of childbearing potential must have negative pregnancy test results at entry.
• Female patients or patients with partners of childbearing potential must agree to use an appropriate method of contraception for a period between acquisition of informed consent and 6 months (180 days) after the final dose so that patients or female partners would not become pregnant.
• AML patients who could not attain remission after 1 or 2 cycles of potent chemotherapy with anthracycline, cytarabine, and etoposide, or potent chemotherapy with anthracycline and cytarabine. Or patients with 1st or 2nd recurrent AML after complete remission following initial therapy.
• Treatment naive AML patients.

You may not qualify if:

• \[For all parts\]
• Diagnosed with acute promyelocytic leukemia (APL) (FAB classification: M3).
• Received a transplantation such as hematopoietic stem cell transplant.
• Have active central nervous system (CNS) leukemia.
• Complicated by ≥ Grade 3 infection as specified in Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).
• HIV antibody, HBs antigen, or HCV antibody tested positive within 90 days prior to entry.
• Have New York Heart Association (NYHA) cardiac function classification III or IV heart disease or a history, ≥ Grade 3 arrhythmia, angina pectoris or abnormal electrocardiogram (ECG) findings as specified in CTCAE v4.03 or a history of these above.
• Have a disease that may interfere with the study treatment, such as interstitial pneumonia, pulmonary fibrosis, or active tuberculosis.
• Complicated by uncontrolled disseminated intravascular coagulation.
• Have other active malignancies (synchronous multiple malignancies and metachronous multiple malignancies with a disease-free interval not more than 5 years. However, carcinoma in situ that is determined to be cured by local treatment or lesions equivalent to mucosal carcinoma are not included in active multiple malignancies.)
• Have an uncontrolled complication.
• Complicated by mental deficits or have a history of mental deficits. However, patients who are able to comply with the study protocol can be included at the discretion of a physician.
• Complicated by varicella.
• Received any previous treatment with DSP-2033 or other CDK inhibitors.
• Received any investigational product or post-marketing clinical study drug within 3 months (90 days) prior to entry.

Sponsors & Collaborators

• Sumitomo Pharma Co., Ltd.: lead

Study Sites (11)

Fukui University Hospital

Yoshida-gun, Fukui, Japan

Location

Chugoku Central Hospital

Fukuyama, Hiroshima, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Location

Tokai University Hospital

Isehara, Kanagawa, Japan

Location

Osaka City Hospital Organization

Miyakojima-ku, Osaka, Japan

Location

Kindai University Hospital

Sayama, Osaka, Japan

Location

NTT Medical Center Tokyo

Shinagawa-ku, Tokyo, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

National Hospital Organization Kyushu Medical Center

Fukuoka, Japan

Location

Fukushima Medical University Hospital

Fukushima, Japan

Location

Related Publications (1)

• Ikezoe T, Ando K, Onozawa M, Yamane T, Hosono N, Morita Y, Kiguchi T, Iwasaki H, Miyamoto T, Matsubara K, Sugimoto S, Miyazaki Y, Kizaki M, Akashi K. Phase I study of alvocidib plus cytarabine/mitoxantrone or cytarabine/daunorubicin for acute myeloid leukemia in Japan. Cancer Sci. 2022 Dec;113(12):4258-4266. doi: 10.1111/cas.15458. Epub 2022 Oct 10.

  PMID: 35689544 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

alvocidib; Cytarabine; Mitoxantrone; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Anthracyclines; Naphthacenes; Aminoglycosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open labeled
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study consists of 2 cohorts of the ACM regimen part and 1 cohort of the A+7+3 regimen part.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: June 20, 2018
• Study Start: May 15, 2018
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: April 12, 2022

Record last verified: 2022-04

Locations

JP (11)