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Acute Myeloid LeukemiaPhase 1NCT00462761

A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status

A Phase 1 study testing AC220 in people with Acute Myeloid Leukemia and Leukemia, run by Daiichi Sankyo at 5 sites in 2 countries.

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

Patients received oral AC220 daily for 14 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3 status. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AC220
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
5 sitesin 2 countries
Study dates
Jan 2007to Dec 2009
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females age ≥ 18 years;
  • Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:
  • Refractory to at least 1 cycle of induction chemotherapy, or
  • Relapsed after at least 1 cycle of induction chemotherapy, or
  • Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
  • Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;
  • Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
  • Serum creatinine ≤ 2.0 mg/dL;
  • Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
  • Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
  • Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
  • Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
  • Written informed consent must be provided.

Who cannot join

  • Histologic diagnosis of acute promyelocytic leukemia;
  • Clinically active central nervous system leukemia;
  • Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);
  • Bone marrow transplant within 2 months prior to study;
  • Active, uncontrolled infection;
  • Major surgery within 4 weeks prior to study;
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  • Radiation therapy within 4 weeks prior to, or concurrent with, study;
  • Human immunodeficiency virus positivity;
  • Active hepatitis B or C or other active liver disease;
  • Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
  • Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States3 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

Georgia2 sites

  • Chemotherapy and Immunotherapy Clinic

    Tbilisi

  • Hematology and Chemotherapy Clinic

    Tbilisi

Other trials in Georgia

About this study

Official title: Phase I Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AC220 When Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia

Patients received oral AC220 daily for 14 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3 status.

Read the detailed description

This is a multi-center clinical study conducted in the USA and two international sites. This open-label, dose escalation study was designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered AC220 as a single agent given daily for 14 days. Cohorts of 3 patients received AC220 until dose limiting toxicity was noted (DLT). At that point cohorts expanded to 6 patients until MTD was determined. Patients not experiencing DLT or significant disease progression at Day 15 may have continued receiving AC220 at the discretion of the Investigator and Sponsor. FLT3 positive and negative patients were allowed to participate.

Being tested
AC220
Keywords
RTK, kinase, inhibitor, tyrosine, acute, FLT3, AC220, pharmacokinetic, pharmacokinetics, PK, pharmacodynamic, pharmacodynamics, mutations, PD, receptor, class III, relapsed, refractory, t(8;21), q22;q22
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelodysplastic Syndromes, Recurrence, Aortic aneurysm, familial thoracic 4, Leukemia, Erythroblastic, Acute, Primary Myelofibrosis

What participants receive

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

  • AC220Drug

    Also called Quizartinib

    Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials. Requires reconstitution by a pharmacist, and must be stored securely and protected from light.

Study groups in NCT00462761
Study groupRoleWhat they receive
AC220ExperimentalDetermine safety, tolerability and pharmacokinetic (PK) parameters of AC220
Receives: Drug: AC220

What is being measured

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

  1. Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Measured: Baseline up to 30 days post last dose

  2. Number of Participants With Treatment-emergent Treatment-related Grade 3 or 4 Adverse Events By At Least 10% of All Participants By Dose Group Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Measured: Baseline up to 30 days post last dose

Secondary outcomes (4)

  1. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Progressive disease response criteria included doubling of blast count % in bone marrow (biopsy or aspirate) from baseline; considering measurements starting on Study Day 15, doubling of blast count % in blood from baseline; death determined to be related to disease or disease progression; and investigator reported disease progression.

    Measured: Baseline up to 28 days after the last dose, up to approximately 3 years

  2. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Complete Response (CR) response criteria included either a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying BM assessment. CRp response included all CR criteria met, except participant did not experience a platelet recovery (ANC recovery required). CRi response included a qualifying BM result, but not an ANC recovery. Participants may or may not have had a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline BM assessment carried out, but results did not meet any response criteria. Participants who were not evaluable (NE) did not have at least 14 days of treatment and were not assessed.

    Measured: Baseline up to 28 days after the last dose, up to approximately 3 years

  3. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Complete Response (CR) response criteria included either a post-baseline bone marrow biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying bone marrow assessment. CRp response included all CR criteria met except participant did not experience a platelet recovery. Participants must have experienced an ANC Recovery. CRi response included a qualifying bone marrow result, but did not experience an ANC recovery. Participants may or may not have experienced a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the bone marrow aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline bone marrow assessment carried out, but results did not meet any of the CR or PR or progressive disease criteria.

    Measured: Baseline up to 28 days after the last dose, up to approximately 3 years

  4. Number of Participants With Hematologic Improvement Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

    Hematologic improvement is summarized in terms of Erythroid Response (HI-E), Platelet Response (HI-P), Neutrophil Response (HI-N), and Hematologic Improvement (HI).

    For post-treatment results, HI-E major responders had >2 g/dL increase in hemoglobin for at least 1 result after first treatment and transfusion independent; minor responders 1 to 2 g/dL increase in hemoglobin for at least 1 result post first treatment and a 50% decrease in red blood cell transfusion requirements. For HI-P, major responders had ≥30 × 10^9/L increase in platelet count and transfusion independent; minor responders had 50% or more increase in platelet count with a net increase between 10 to 30 × 10^9/L and 50% decrease in platelet transfusion requirements. For HI-N, major responders had an increase in absolute neutrophil count (ANC) of 100% or an absolute increase of more than 0.5 × 10^9/L (whichever is greater); minor responders had an increase in ANC of 100% but an absolute increase of <0.5 × 10^9/L.

    Measured: Baseline up to 28 days after the last dose, up to approximately 3 years

Timeline

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

  1. First posted19 Apr 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionMar 2009
  4. Study completionDec 2009

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00462761
Sponsor's protocol ID
CP0001
Status last verified
Apr 2020
First submitted
17 Apr 2007
Last updated
11 May 2020
Data monitoring committee
No
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

  • Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3.

    PubMed 24002496

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AC220 in people with Acute Myeloid Leukemia and Leukemia, run by Daiichi Sankyo at 5 sites in 2 countries.

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 15 inclusion and 11 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 11 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Georgia. 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?

Yes. Results are posted in the registry (first posted 24 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia (time frame: Baseline up to 30 days post last dose). The study lists 2 primary outcomes in all. 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 NCT00462761, 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 11 May 2020.

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