Clinical Trials /

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

NCT03563560

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of DSP-2033 (Alvocidib) in Patients With Acute Myeloid Leukemia
  • Official Title: A Phase 1 Clinical Study of DSP-2033 (Alvocidib) in Combination With Cytarabine/Mitoxantrone or Cytarabine/Daunorubicin (7+3) in Patients With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: DC850101
  • NCT ID: NCT03563560

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AlvocidibDSP-2033ACM regimen
CytarabineDSP-AraCACM regimen
MitoxantroneDSP-MITACM regimen
CytarabineA+7+3 regimen
DaunorubicineDSP-DNRA+7+3 regimen

Purpose

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).

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.

        1. 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.

        2. 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.
    

Trial Arms

NameTypeDescriptionInterventions
ACM regimenExperimentalACM regimen is for Japanese patients with relapsed or refractory AML.
  • Alvocidib
  • Cytarabine
  • Mitoxantrone
A+7+3 regimenExperimentalA+7+3 regimen is for Japanese newly diagnosed AML patients.
  • Alvocidib
  • Cytarabine
  • Daunorubicine

Eligibility Criteria

        Inclusion Criteria:

        [For all parts]

          1. Japanese patients diagnosed with AML by the 4th edition of WHO criteria.

          2. Patients aged between 20 and 64 at acquisition of informed consent.

          3. 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.

          4. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 at
             entry.

          5. Have a left ventricular ejection fraction (LVEF) ≥ 50% determined by echocardiography
             or multigated acquisition (MUGA) scan within 14 days prior to entry.

          6. Have an arterial oxygen saturation (SpO2) ≥ 90% within 14 days prior to entry.

          7. 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.

               1. Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) of the institutional
                  reference standard

               2. AST and ALT ≤ 2 x ULN of the institutional reference standard

               3. Total bilirubin ≤ 2.0 mg/dL

          8. Female patients of childbearing potential must have negative pregnancy test results at
             entry.

          9. 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.

         10. 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

         11. Treatment naive AML patients.

        Exclusion Criteria:

        [For all parts]

          1. Diagnosed with acute promyelocytic leukemia (APL) (FAB classification: M3).

          2. Received a transplantation such as hematopoietic stem cell transplant.

          3. Have active central nervous system (CNS) leukemia.

          4. Complicated by ≥ Grade 3 infection as specified in Common Terminology Criteria for
             Adverse Events version 4.03 (CTCAE v4.03).

          5. HIV antibody, HBs antigen, or HCV antibody tested positive within 90 days prior to
             entry.

          6. 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.

          7. Have a disease that may interfere with the study treatment, such as interstitial
             pneumonia, pulmonary fibrosis, or active tuberculosis.

          8. Complicated by uncontrolled disseminated intravascular coagulation.

          9. 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.)

         10. Have an uncontrolled complication.

         11. 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.

         12. Complicated by varicella.

         13. Received any previous treatment with DSP-2033 or other CDK inhibitors.

         14. Received any investigational product or post-marketing clinical study drug within 3
             months (90 days) prior to entry.

         15. 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.

         16. 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.

         17. Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose,
             exceeds 360 mg/m2 (body surface area) at entry.

         18. Received other leukemia treatment within 21 days prior to entry.

         19. Have a history of radiation therapy on the mediastinum.

         20. Have sustained ≥ Grade 2 adverse drug reaction (except alopecia) as specified in CTCAE
             v4.03, which developed by the previous treatment.

         21. 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.

         22. Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose,
             exceeds 100 mg/m2 (body surface area) at entry.

         23. Have a history of hypersensitivity against any one of cytarabine, daunorubicin, or
             contained excipients.
      
Maximum Eligible Age:64 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0
Time Frame:2 months
Safety Issue:
Description: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

Measure:To evaluate peak plasma concentration (Cmax) of ACM regimen and A+7+3 regimen in Japanese
Time Frame:14 days
Safety Issue:
Description: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.
Measure:To evaluate Area under the plasma concentration versus time curve (AUC) of ACM regimen and A+7+3 regimen in Japanese
Time Frame:14 days
Safety Issue:
Description: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.
Measure:To evaluate the Anti-tumor effects based on bone-marrow blasts
Time Frame:2 months
Safety Issue:
Description: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)
Measure:Event-free survival (EFS) (ACM regimen part only)
Time Frame:12 months
Safety Issue:
Description:EFS of ACM regimen in Japanese patients with relapsed or refractory AML.
Measure:Overall survival (OS) (ACM regimen part only)
Time Frame:12 months
Safety Issue:
Description:OS of ACM regimen in Japanese patients with relapsed or refractory AML.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sumitomo Dainippon Pharma Co., Ltd.

Trial Keywords

  • Newly diagnosed AML
  • Relapsed/refractory AML
  • Alvocidib

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