A Trial to Establish the Feasibility of Combining Either the Tyrosine Kinase Inhibitor AC220,CXCR4 Inhibitor Plerixafor or HSP90 Inhibitor Ganetespib With Chemotherapy in Older Patients With Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome. (AML18 Pilot)

This study is currently recruiting participants.
Verified April 2013 by Cardiff University
Sponsor:
Collaborators:
Leukaemia & Lymphoma Research Group
Experimental Cancer Medicine Centre Network
Information provided by (Responsible Party):
Alan K Burnett, Cardiff University
ClinicalTrials.gov Identifier:
NCT01236144
First received: November 5, 2010
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

The AML18 Pilot Trial will evaluate the feasibility of three interventions that are planned to be included in the forthcoming NCRI AML18 Trial. One intervention will be to evaluate combining the Tyrosine Kinase Inhibitor AC220 with three courses of standard DAE (Daunorubicin, Ara-C, Etoposide). AC220 will be given following each treatment course, daily by mouth for 7, 14 or 21 days. AC220 will be evaluated at 3 dose levels of 60, 90 and 135 mg flat dose. A 4th dose level of 40 mg will be introduced should patients not respond well to 60 mg. The second intervention to be tested is the combination of the CXCR4 inhibitor Plerixafor with up to three courses of the chemotherapy combination of DClo (Daunorubicin, Clofarabine). Patients/investigators will be able to choose which intervention to enter. Depending on recruitment requirements, only one intervention might be available at any one time. The third intervention Patients will receive 3 treatments of 100 mg of ganetespib on days 1, 8 and 15 of each course where day 1 is the first day of the chemotherapy. The chemotherapy will be DAE/DAE/DA. Three courses of chemotherapy will be given each of which will be associated with 3 administrations of ganetespib.


Condition Intervention Phase
Acute Myeloid Leukaemia
High Risk Myelodysplastic Syndrome
Drug: Plerixafor
Drug: AC220
Drug: Ganetespib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An NCRI Acute Myeloid Leukaemia Working Group Pilot Trial Under the Auspices of the Cardiff Experimental Cancer Medicine Centre to Establish the Feasibility of Combining Either the Tyrosine Kinase Inhibitor AC220,CXCR4 Inhibitor Plerixafor or HSP90 Inhibitor Ganetespib With Chemotherapy in Older Patients With Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome.

Resource links provided by NLM:


Further study details as provided by Cardiff University:

Primary Outcome Measures:
  • Response (CR, CRi, PR) achievement, and reasons for failure [ Time Frame: Duration of treatment ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: At 30 days and 8 weeks ] [ Designated as safety issue: No ]
  • Toxicity (haematological and non-haematological) [ Time Frame: Duration of trial treatment ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: At 6 and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: April 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AC220 Intervention Drug: AC220
Each cohort of patients will receive three courses of chemotherapy approximately 4 to 5 weeks apart which will comprise of Daunorubicin/Ara-C/Etoposide in Courses 1&2 and Daunorubicin/Ara-C in Course 3. Two days after the last day of each chemotherapy course, patients will receive AC220 orally for 7, 14 or 21 (depending on cohort) consecutive days. Depending on which cohort the patient enters, they will receive either 60mg, 90mg or 135mg of AC220 daily, with a provision to assess 40mg if necessary.
Experimental: Plerixafor Intervention Drug: Plerixafor
Fixed dose of Plerixafor (240mcg/kg) given by subcutaneous injection on each day of chemotherapy for up to 3 courses (depending on cohort). The three chemotherapy courses will be Daunorubicin/Clofarabine for courses 1&2 and Daunorubicin/Ara-C for course 3. Each course will last 5 days, and Plerixafor will be given for 5 days.
Other Name: Mozobil
Experimental: Ganetespib Drug: Ganetespib
Patients will receive 3 treatments of ganetespib on days 1, 8 and 15 of each course where day 1 is the first day of the chemotherapy. The chemotherapy will be DAE/DAE/DA. Three courses of chemotherapy will be given each of which will be associated with 3 administrations of ganetespib.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • They have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia or CML in blast crisis as defined by the WHO Classification (Appendix A) — this can be any type of de novo or secondary AML - or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2).
  • Serum creatinine ≤ 1.5 × ULN (upper limit of normal)
  • White cell count of <30 x 109/L at diagnosis (for Plerixafor option only). If WCC is >30 x 109/l patients in the Plerixafor pilot should have the WCC reduced to <30 x 109/L using Hydroxycarbamide to avoid the risk of hyperleucocytosis
  • Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits, and every effort should be made to keep potassium at institutional normal limits, and every effort should be made to keep potassium concentrations above 4.0 mEq/dL, and serum calcium at normal concentration.
  • Total serum bilirubin ≤ 1.5 × ULN (upper limit of normal) and serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5 × ULN
  • Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if their sexual partners are women of child bearing potential (WOCBP).
  • Over 60 years of age
  • Provided written informed consent

Exclusion Criteria:

  • They have previously received cytotoxic chemotherapy for AML. [Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion].
  • They are in blast transformation of chronic myeloid leukaemia (CML).
  • They have a concurrent active malignancy excluding basal cell carcinoma.
  • They are pregnant or lactating.
  • They have Acute Promyelocytic Leukaemia
  • Known infection with human immunodeficiency virus (HIV)

Patients are not eligible for the AC220 option if they have:

  • Uncontrolled or significant cardiovascular disease, including :
  • A myocardial infarction within 12 months
  • Uncontrolled angina within 6 months
  • Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless an echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is ≥ 45% (or institutional lower limit of normal value).
  • Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes [TdP]); any history of arrhythmia will be discussed with the Sponsor's Medical Monitor prior to patient's entry into the study.
  • Prolonged QTcF interval on pre-entry ECG (≥450 ms) - this will be the average of 3 readings within a 2 hour period.
  • Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker).
  • Heart rate < 50/minute on pre-entry ECG
  • Uncontrolled hypertension
  • Obligate need for a cardiac pacemaker
  • Complete left bundle branch block
  • Atrial fibrillation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01236144

Locations
United Kingdom
Aberdeen Royal Infirmary Recruiting
Aberdeen, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Dominic Culligan         
Belfast City Hospital Not yet recruiting
Belfast, United Kingdom
Principal Investigator: Mary-Frances McMullin         
Birmingham Heartlands Hospital Recruiting
Birmingham, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Don Milligan         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Jenny Craig         
University Hospital of Wales Recruiting
Cardiff, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Steven Knapper         
Castle Hill Hospital Recruiting
Hull, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Sara Ali         
St James's University Hospital Recruiting
Leeds, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: David Bowen         
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Richard Clark         
St Bartholomew's Hospital Not yet recruiting
London, United Kingdom
Principal Investigator: Matthew Smith         
Manchester Royal Infirmary Recruiting
Manchester, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: John Yin         
Christie Hospital Not yet recruiting
Manchester, United Kingdom
Principal Investigator: Mike Dennis         
Freeman Hospital Not yet recruiting
Newcastle, United Kingdom
Principal Investigator: Gail Jones         
Nottingham University Hospital Recruiting
Nottingham, United Kingdom
Contact: Sarah Burns       burnss1@cardiff.ac.uk   
Principal Investigator: Nigel Russell         
Sponsors and Collaborators
Cardiff University
Leukaemia & Lymphoma Research Group
Experimental Cancer Medicine Centre Network
Investigators
Study Chair: Alan K Burnett Cardiff University
Study Chair: Nigel H Russell Nottingham University
  More Information

No publications provided

Responsible Party: Alan K Burnett, Chief Investigator, Cardiff University
ClinicalTrials.gov Identifier: NCT01236144     History of Changes
Other Study ID Numbers: SPON 845-10, 2010-021444-18, 10/MRE09/27
Study First Received: November 5, 2010
Last Updated: April 25, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cardiff University:
Myeloid
Leukaemia
Acute
Myelodysplastic
Pilot
Cardiff
Haematology
Burnett
AC220
Plerixafor
Ganetespib

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014