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)

NCT00486265 | Terminated Phase 1 Results

• 1 other identifier: D2782C00007
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 4

Brief 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). For enrollment information see the Central Contact information below

Conditions

Acute Myelogenous Leukemia

Keywords

Phase I; Phase II; acute myelogenous leukemia; AML; cancer

Outcome Measures

Primary Outcomes (3)

• 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)

  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.

  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

  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)

  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

  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.

Interventions

AZD4877 DRUG

intravenous infusion administered on days 1, 2 and 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Chicago, Illinois, United States

Location

Research Site

Houston, Texas, United States

Location

Research Site

San Antonio, Texas, United States

Location

Research Site

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 21494838 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

N-(3-aminopropyl)-N-(1-(5-benzyl-3-methyl-4-oxo-(1,2)thiazolo(5,4-d)pyrimidin-6-yl)-2-methylpropyl)-4-methylbenzamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Study Officials

• Gregory A Curt, MD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 13, 2007
• First Posted: June 14, 2007
• Study Start: July 1, 2007
• Study Completion: July 1, 2009
• Last Updated: December 21, 2010
• Results First Posted: August 17, 2010

Record last verified: 2010-07

Locations

CA (1); US (3)