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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03563560
Recruitment Status : Active, not recruiting
First Posted : June 20, 2018
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Co., Ltd.

Tracking Information
First Submitted Date  ICMJE March 21, 2018
First Posted Date  ICMJE June 20, 2018
Last Update Posted Date February 28, 2020
Actual Study Start Date  ICMJE May 15, 2018
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
  • To evaluate peak plasma concentration (Cmax) of ACM regimen and A+7+3 regimen in Japanese [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 12 months ]
    EFS of ACM regimen in Japanese patients with relapsed or refractory AML.
  • Overall survival (OS) (ACM regimen part only) [ Time Frame: 12 months ]
    OS of ACM regimen in Japanese patients with relapsed or refractory AML.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of DSP-2033 (Alvocidib) in Patients With Acute Myeloid Leukemia
Official Title  ICMJE 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
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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
This study consists of 2 cohorts of the ACM regimen part and 1 cohort of the A+7+3 regimen part.
Masking: None (Open Label)
Masking Description:
Open labeled
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • 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 Name: DSP-2033
  • Drug: Cytarabine
    300 or 667 mg/m2/day, 72-hour continuous IV infusion starting on Day 6 (ACM regimen)
    Other Name: DSP-AraC
  • 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 Name: DSP-MIT
  • 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 Name: DSP-DNR
Study Arms  ICMJE
  • Experimental: ACM regimen
    ACM regimen is for Japanese patients with relapsed or refractory AML.
    Interventions:
    • Drug: Alvocidib
    • Drug: Cytarabine
    • Drug: Mitoxantrone
  • Experimental: A+7+3 regimen
    A+7+3 regimen is for Japanese newly diagnosed AML patients.
    Interventions:
    • Drug: Alvocidib
    • Drug: Cytarabine
    • Drug: Daunorubicine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 13, 2018)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03563560
Other Study ID Numbers  ICMJE DC850101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumitomo Dainippon Pharma Co., Ltd.
Study Sponsor  ICMJE Sumitomo Dainippon Pharma Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sumitomo Dainippon Pharma Co., Ltd.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP