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Acute Myeloid LeukemiaPhase 1AMLNCT03563560

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

A Phase 1 study testing Alvocidib, Cytarabine and Mitoxantrone in people with Acute Myeloid Leukemia, run by Sumitomo Pharma Co., Ltd. at 11 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 20 to 64 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Alvocidib, Cytarabine and Mitoxantrone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
11 sitesJapan
Study dates
15 May 2018to 31 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • [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.
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  • 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.
  • [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.

Who cannot join

  • [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.
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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.
  • 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.
  • 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.
  • Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 360 mg/m2 (body surface area) at entry.
  • Received other leukemia treatment within 21 days prior to entry.
  • Have a history of radiation therapy on the mediastinum.
  • Have sustained ≥ Grade 2 adverse drug reaction (except alopecia) as specified in CTCAE v4.03, which developed by the previous treatment.
  • 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.
  • Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 100 mg/m2 (body surface area) at entry.
  • Have a history of hypersensitivity against any one of cytarabine, daunorubicin, or contained excipients.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Japan11 sites

  • Kyushu University Hospital

    Fukuoka

  • National Hospital Organization Kyushu Medical Center

    Fukuoka

  • Fukushima Medical University Hospital

    Fukushima

  • Chugoku Central Hospital

    Fukuyama, Hiroshima

  • Tokai University Hospital

    Isehara, Kanagawa

  • Osaka City Hospital Organization

    Miyakojima-ku, Osaka

  • Hokkaido University Hospital

    Sapporo, Hokkaido

  • Kindai University Hospital

    Sayama, Osaka

  • NTT Medical Center Tokyo

    Shinagawa-ku, Tokyo

  • University of Tsukuba Hospital

    Tsukuba, Ibaraki

  • Fukui University Hospital

    Yoshida-gun, Fukui

Other trials in Japan

About this study

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

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).

Read the 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.
Being tested
Alvocidib, Cytarabine, Mitoxantrone, Daunorubicine
Keywords
Newly diagnosed AML, Relapsed/refractory AML, Alvocidib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlvocidibDrug

    Also called DSP-2033

    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

  • CytarabineDrug

    Also called DSP-AraC

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

  • MitoxantroneDrug

    Also called DSP-MIT

    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)

  • CytarabineDrug

    100 mg/m2/day, continuous IV infusion for 7 days from Day 5 to Day 11 (A+7+3 regimen)

  • DaunorubicineDrug

    Also called DSP-DNR

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

Study groups in NCT03563560
Study groupRoleWhat they receive
ACM regimenExperimentalACM regimen is for Japanese patients with relapsed or refractory AML.
Receives: Drug: Alvocidib; Drug: Cytarabine; Drug: Mitoxantrone
A+7+3 regimenExperimentalA+7+3 regimen is for Japanese newly diagnosed AML patients.
Receives: Drug: Alvocidib; Drug: Cytarabine; Drug: Daunorubicine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 months

Secondary outcomes (5)

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

    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.

    Measured: 14 days

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

    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.

    Measured: 14 days

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

    • 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)

    Measured: 2 months

  4. Event-free survival (EFS) (ACM regimen part only)

    EFS of ACM regimen in Japanese patients with relapsed or refractory AML.

    Measured: 12 months

  5. Overall survival (OS) (ACM regimen part only)

    OS of ACM regimen in Japanese patients with relapsed or refractory AML.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2018
  2. Study start15 May 2018
  3. Primary completion31 Mar 2020
  4. Study completion31 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
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)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03563560
Sponsor's protocol ID
DC850101
Acronym
AML
Status last verified
Apr 2022
First submitted
21 Mar 2018
Last updated
12 Apr 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 35689544

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alvocidib, Cytarabine and Mitoxantrone in people with Acute Myeloid Leukemia, run by Sumitomo Pharma Co., Ltd. at 11 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0 (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03563560, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.

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