AML: A Study of DSP-2033 (Alvocidib) in Patients With Acute Myeloid Leukemia
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This study consists of 2 cohorts of the ACM regimen part for Japanese relapsed/refractory AML patients and 1 cohort of the A+7+3 regimen part for Japanese newly diagnosed AML patients. The purpose of this study are as below.
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To evaluate the safety of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) in Japanese patients with relapsed or refractory AML and to confirm its tolerability.
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To evaluate the safety of DSP-2033 （Alvocidib) in combination with cytarabine/daunorubicin (A+7+3 regimen) in Japanese newly diagnosed AML patients and to confirm its tolerability.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ACM regimen ACM regimen is for Japanese patients with relapsed or refractory AML. |
Drug: Alvocidib
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
Other Names:
Drug: Cytarabine
300 or 667 mg/m2/day, 72-hour continuous IV infusion starting on Day 6 (ACM regimen)
Other Names:
Drug: Mitoxantrone
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)
Other Names:
|
| Experimental: A+7+3 regimen A+7+3 regimen is for Japanese newly diagnosed AML patients. |
Drug: Alvocidib
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
Other Names:
Drug: Cytarabine
100 mg/m2/day, continuous IV infusion for 7 days from Day 5 to Day 11 (A+7+3 regimen)
Drug: Daunorubicine
60 mg/m2/day, 30-minute IV infusion for 3 days from Day 5 to Day 7
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0 [2 months]
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.
Secondary Outcome Measures
- To evaluate peak plasma concentration (Cmax) of ACM regimen and A+7+3 regimen in Japanese [14 days]
Pharmacokinetics of individual drugs of ACM regimen in Japanese patients with relapsed or refractory AML and A+7+3 regimen in Japanese newly diagnosed AML patients. Pharmacokinetic analyses:Pharmacokinetic parameters of Maximum Plasma Concentration [Cmax] DSP-2033, DSP-2033 glucuronide (Alvo-G), cytarabine, mitoxantrone, and daunorubicin.
- To evaluate Area under the plasma concentration versus time curve (AUC) of ACM regimen and A+7+3 regimen in Japanese [14 days]
Pharmacokinetics of individual drugs of ACM regimen in Japanese patients with relapsed or refractory AML and A+7+3 regimen in Japanese newly diagnosed AML patients. Pharmacokinetic analyses:Pharmacokinetic parameters of Area Under the Curve [AUC] DSP-2033, DSP-2033 glucuronide (Alvo-G), cytarabine, mitoxantrone, and daunorubicin.
- To evaluate the Anti-tumor effects based on bone-marrow blasts [2 months]
Complete remission rate (CR rate) CR with incomplete hematologic recovery (CRi rate) Combined Complete remission rate (CRc rate): a total of CR rate and CRi rate Partial remission rate (PR rate) (Evaluated by 2017 European Leukemia Net AML efficacy assessment criteria)
- Event-free survival (EFS) (ACM regimen part only) [12 months]
EFS of ACM regimen in Japanese patients with relapsed or refractory AML.
- Overall survival (OS) (ACM regimen part only) [12 months]
OS of ACM regimen in Japanese patients with relapsed or refractory AML.
Eligibility Criteria
Criteria
Inclusion Criteria:
[For all parts]
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Japanese patients diagnosed with AML by the 4th edition of WHO criteria.
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Patients aged between 20 and 64 at acquisition of informed consent.
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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.
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Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 at entry.
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Have a left ventricular ejection fraction (LVEF) ≥ 50% determined by echocardiography or multigated acquisition (MUGA) scan within 14 days prior to entry.
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Have an arterial oxygen saturation (SpO2) ≥ 90% within 14 days prior to entry.
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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.
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Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) of the institutional reference standard
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AST and ALT ≤ 2 x ULN of the institutional reference standard
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Total bilirubin ≤ 2.0 mg/dL
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Female patients of childbearing potential must have negative pregnancy test results at entry.
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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.
[ACM regimen part] In addition to the inclusion criteria for all parts, patients must meet the following criterion.
- 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.
[A+7+3 regimen part] In addition to the inclusion criteria for all parts, patients must meet the following criterion
- Treatment naive AML patients.
Exclusion Criteria:
[For all parts]
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Diagnosed with acute promyelocytic leukemia (APL) (FAB classification: M3).
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Received a transplantation such as hematopoietic stem cell transplant.
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Have active central nervous system (CNS) leukemia.
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Complicated by ≥ Grade 3 infection as specified in Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).
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HIV antibody, HBs antigen, or HCV antibody tested positive within 90 days prior to entry.
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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.
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Have a disease that may interfere with the study treatment, such as interstitial pneumonia, pulmonary fibrosis, or active tuberculosis.
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Complicated by uncontrolled disseminated intravascular coagulation.
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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.)
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Have an uncontrolled complication.
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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.
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Complicated by varicella.
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Received any previous treatment with DSP-2033 or other CDK inhibitors.
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Received any investigational product or post-marketing clinical study drug within 3 months (90 days) prior to entry.
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Pregnant or lactating women*)
*) If a lactating woman agrees to discontinue breast feeding between acquisition of informed consent and 6 months (180 days) after the final dose, she could be included in the study.
- Patients who are determined to be inappropriate for participation in this study by the investigator or subinvestigator.
[ACM regimen part] In addition to the exclusion criteria cfor all parts, patients who meet any one of the following criteria 17 to 21 will be excluded from the ACM regimen part.
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Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 360 mg/m2 (body surface area) at entry.
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Received other leukemia treatment within 21 days prior to entry.
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Have a history of radiation therapy on the mediastinum.
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Have sustained ≥ Grade 2 adverse drug reaction (except alopecia) as specified in CTCAE v4.03, which developed by the previous treatment.
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Have a history of hypersensitivity against any one of cytarabine, mitoxantrone, or contained excipients.
[A+7+3 regimen part] In addition to the exclusion criteria for all parts, patients who meet any one of the following criteria 22 to 23 will be excluded from the A+7+3 regimen part.
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Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 100 mg/m2 (body surface area) at entry.
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Have a history of hypersensitivity against any one of cytarabine, daunorubicin, or contained excipients.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fukui University Hospital | Yoshida-gun | Fukui | Japan | |
| 2 | Chugoku Central Hospital | Fukuyama | Hiroshima | Japan | |
| 3 | Hokkaido University Hospital | Sapporo | Hokkaido | Japan | |
| 4 | University of Tsukuba Hospital | Tsukuba | Ibaraki | Japan | |
| 5 | Tokai University Hospital | Isehara | Kanagawa | Japan | |
| 6 | Osaka City Hospital Organization | Miyakojima-ku | Osaka | Japan | |
| 7 | Kindai University Hospital | Osakasayama | Osaka | Japan | |
| 8 | NTT Medical Center Tokyo | Shinagawa-ku | Tokyo | Japan | |
| 9 | Kyushu University Hospital | Fukuoka | Japan | ||
| 10 | National Hospital Organization Kyushu Medical Center | Fukuoka | Japan | ||
| 11 | Fukushima Medical University Hospital | Fukushima | Japan |
Sponsors and Collaborators
- Sumitomo Pharma Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DC850101