Acute Myelogenous LeukemiaPhase 1NCT00486265

Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)

A Phase 1 study testing AZD4877 in people with Acute Myelogenous Leukemia, run by AstraZeneca at 4 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD4877 based on the side effects experienced by patients that receive AZD4877 on a daily times 3 schedule in acute myelogenous leukemia (AML). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myelogenous Leukemia
What is being tested?: AZD4877
Type of treatment: Injection or infusion
How many people: 47 participants
Where: 4 sitesin 2 countries
Study dates: Jul 2007to Jul 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

Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission
Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment.
Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy

Who cannot join

Promyelocytic acute myelogenous leukemia
Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation.
Liver injury

Trial locations and contacts

4 sites in 2 countries.

Country

City, postcode or hospital

4 sites in 2 countries

United States3 sites

Research Site
Chicago, Illinois
Research Site
Houston, Texas
Research Site
San Antonio, Texas

Other trials in United States

Canada1 site

Research Site
Toronto, Ontario

Other trials in Canada

About this study

Official title: A Phase I/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML) Excluding Promyelocytic Leukemia

For enrollment information see the Central Contact information below

Conditions: Acute Myelogenous Leukemia
Being tested: AZD4877
Keywords: Phase I, Phase II, acute myelogenous leukemia, AML, cancer
Medical subject headings: Leukemia, Myeloid, Acute, Neoplasms

What participants receive

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

AZD4877Drug
intravenous infusion administered on days 1, 2 and 3

What is being measured

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

To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
Measured: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Measured: Response is evaluated after a maximum of 2 courses of induction therapy.
To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
Maximum plasma concentration, Cmax
Measured: PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.

Secondary outcomes (2)

To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Measured: Response is evaluated after a maximum of 2 courses of induction therapy.
To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs
Measured: Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible.

Timeline

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

Jul 2007Jul 2009

First posted14 Jun 2007 (estimated)
Study startJul 2007
Study completionJul 2009

Why it stopped: AML assess. of response in Part B patients find treatment failure in all 8 evaluable for marrow response following a maximum of 2 induction courses of therapy

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00486265
Sponsor's protocol ID: D2782C00007
Status last verified: Jul 2010
First submitted: 13 Jun 2007
Last updated: 21 Dec 2010
Results posted: Yes, on ClinicalTrials.gov

Publications

Kantarjian HM, Padmanabhan S, Stock W, Tallman MS, Curt GA, Li J, Osmukhina A, Wu K, Huszar D, Borthukar G, Faderl S, Garcia-Manero G, Kadia T, Sankhala K, Odenike O, Altman JK, Minden M. Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia. Invest New Drugs. 2012 Jun;30(3):1107-15. doi: 10.1007/s10637-011-9660-2. Epub 2011 Apr 15.
PubMed 21494838

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1/2
A Study of Sonrotoclax (BGB-11417) in Children With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia
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MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 2
Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia
RecruitingPhase 2
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
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All Acute Myelogenous Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML) Excluding Promyelocytic Leukemia
ClinicalTrials.gov ID: NCT00486265
Acronym / sponsor ID: D2782C00007
Conditions: Acute Myelogenous Leukemia
Keywords: Phase I, Phase II, acute myelogenous leukemia, AML, cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: AML assess. of response in Part B patients find treatment failure in all 8 evaluable for marrow response following a maximum of 2 induction courses of therapy
Enrolment: 47 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jul 2007
Study completion: Jul 2009 (actual)
First posted: 14 Jun 2007 (estimated)
Results: Posted 17 Aug 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

For enrollment information see the Central Contact information below

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission
Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment.
Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy

Key exclusion criteria (3 listed)

Promyelocytic acute myelogenous leukemia
Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation.
Liver injury

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD4877intravenous infusion administered on days 1, 2 and 3	Drug	–

Primary outcome

To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
Time frame: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
Time frame: Response is evaluated after a maximum of 2 courses of induction therapy.
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
Time frame: PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.
Maximum plasma concentration, Cmax

2 secondary outcomes

To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
Time frame: Response is evaluated after a maximum of 2 courses of induction therapy.
To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs
Time frame: Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible.

Results and safety

Results posted to the registry on 17 Aug 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD4877	9	0

Primary outcome: To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)

Time frame: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.. Number. Unit: Participants

The sponsor has not posted figures for this outcome.

Primary outcome: To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)

Time frame: Response is evaluated after a maximum of 2 courses of induction therapy.. Number. Unit: Participants

Measure	AZD4877 n = 8
Value	0

Population analysed: 8 of 9 patients in Part B were evaluable for response following a maximum of 2 courses of induction therapy.

Primary outcome: To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]

Time frame: PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.. Geometric mean (Standard Deviation). Unit: ng/mL

The sponsor has not posted figures for this outcome.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD4877	3 of 9 (33.3%)	9 of 9 (100%)	Not reported

Limitations and caveats (from the sponsor): On 16 June 2009, the study was terminated for a lack of efficacy. None of the 8 patients had experienced CR or CRi. The secondary efficacy outcome measures were not evaluated due to early termination and small number of participants.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2010.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21494838Kantarjian HM, Padmanabhan S, Stock W, Tallman MS, Curt GA, Li J, Osmukhina A, Wu K, Huszar D, Borthukar G, Faderl S, Garcia-Manero G, Kadia T, Sankhala K, Odenike O, Altman JK, Minden M. Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia. Invest New Drugs. 2012 Jun;30(3):1107-15. doi: 10.1007/s10637-011-9660-2. Epub 2011 Apr 15.

Related trials for Acute Myelogenous Leukemia

Not yet recruitingPhase 1/2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gregory A Curt, MD study director

AstraZeneca

4 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD4877 in people with Acute Myelogenous Leukemia, run by AstraZeneca at 4 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 3 inclusion and 3 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: stopped early, as of the sponsor's last update on 21 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada. 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 17 Aug 2010). 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?

To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs) (time frame: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.). The study lists 3 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 NCT00486265, 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 21 Dec 2010.