AzTrials
AzTrials

Acute Myeloid LeukaemiaPhase 1/2AML18 PilotNCT01236144

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.

A Phase 1/2 study testing Plerixafor, AC220 and Ganetespib in people with Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome, run by Cardiff University at 13 sites in United Kingdom.

Completed

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

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Plerixafor, AC220 and Ganetespib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
113 participants
Where
13 sitesUnited Kingdom
Study dates
Apr 2011to Jan 2014
Phase
Phase 1/2
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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 19Show fewer
  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United Kingdom13 sites

  • Aberdeen Royal Infirmary

    Aberdeen

  • Belfast City Hospital

    Belfast

  • Birmingham Heartlands Hospital

    Birmingham

  • Addenbrooke's Hospital

    Cambridge

  • University Hospital of Wales

    Cardiff

  • Castle Hill Hospital

    Hull

  • St James's University Hospital

    Leeds

  • Royal Liverpool University Hospital

    Liverpool

  • St Bartholomew's Hospital

    London

  • Christie Hospital

    Manchester

  • Manchester Royal Infirmary

    Manchester

  • Freeman Hospital

    Newcastle

  • Nottingham University Hospital

    Nottingham

Other trials in United Kingdom

About this study

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.

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.

Read the detailed description

The AML18 Pilot Trial is available to any patient who has primary or secondary AML as defined by the WHO Classification (Appendix A) (excluding Acute Promyelocytic Leukaemia), or high risk Myelodysplastic Syndrome (i.e. > 10% marrow blasts) who is not considered suitable for the current NCRI trial for younger patients (MRC AML 17). This trial has the primary aim of assessing the feasibility of three treatments that are planned for the forthcoming NCRI AML18 Trial. The first is the feasibility of adding AC220, given sequentially initially for 7 days, to three courses of standard chemotherapy. AC220 will be assessed at up to three daily dose levels: - 60mg/day, 90mg/day, 135 mg/day and also, if required, at 40mg/day. The protocol will also assess in a separate study cohort the feasibility of combining the CXCR4 inhibitor, Plerixafor, at a fixed dose in combination with up to three courses of chemotherapy. The third intervention 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.

THERAPEUTIC INTERVENTIONS

Therapeutic Interventions for AC220 Assessment:

Patients will enter one of 3 dose level cohorts either 60mg/day, 90mg/day or 135mg/day with the provision to assess 40mg/day if required. Each cohort will receive three courses of chemotherapy approximately 4 to 5 weeks apart, which will comprise DAE ( Daunorubicin, Ara-C, Etoposide) over 10 days (Course 1) , DAE over 8 days (Course 2) and DA (Daunorubicin, Ara-C) over 5 days (Course 3). Two days after the last day of chemotherapy patients will receive the AC220 orally, daily for 7 consecutive days. Formal safety and pharmaco-kinetic assessments will be undertaken on day 1, 7 and 14 of each course of AC220, and interim toxicities will also be required to be reported. Sufficient patients must enter each AC220 dose level cohort to ensure that at least 3 patients are evaluable for all three courses. Cohort 2 (i.e.60mg/day for 14 days) can open to recruitment after a minimum of 3 evaluable patients have completed course 1. Cohort 3 (40mg/day dose level for either 7/14 days) will be undertaken if cohort 1 or 2 are unsuccessful i.e. fail to satisfy the safety criteria.

It is anticipated that the 'study dose' will be established from the experience of cohorts 1 to 5. Cohort 6 ('study dose') will receive AC220 for 21 days after each chemotherapy course. In this cohort there must be a minimum of a 10 days break between the end of the AC220 course and the start of the subsequent chemotherapy course.

Therapeutic Interventions for Plerixafor Assessment:

The aim is to assess the feasibility of combining a fixed dose (240mcg/kg) of Plerixafor given on each day of chemotherapy for up to 3 courses, and if so to combine this with G-CSF in courses 2 and 3. The three chemotherapy courses will be Daunorubicin/Clofarabine (DClo) for courses 1 \& 2 and Daunorubicin/Ara-C (DA) for course 3. Each course will last 5 days and Plerixafor will be given for 5 days.

Cohort 1 will receive three courses of chemotherapy with Plerixafor in course 1 only. Cohort 2 will receive three courses with Plerixafor in course 1 and 2. Cohort 3 will receive chemotherapy with Plerixafor in all three courses. Cohort 4 will be the same as cohort 3 but they will also receive G-CSF in course 2 and 3.

Therapeutic Interventions for Ganetespib Assessment:

There will be one feasibility cohort of 10 evaluable patients who require to be evaluable after 30 days after the first course, where day 1 is the first day of chemotherapy. 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.

Being tested
Plerixafor, AC220, Ganetespib
Keywords
Myeloid, Leukaemia, Acute, Myelodysplastic, Pilot, Cardiff, Haematology, Burnett, AC220, Plerixafor, Ganetespib
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

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

  • PlerixaforDrug

    Also called Mozobil

    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.

  • AC220Drug

    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.

  • GanetespibDrug

    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.

Study groups in NCT01236144
Study groupRoleWhat they receive
AC220 InterventionExperimentalNot described
Receives: Drug: AC220
Plerixafor InterventionExperimentalNot described
Receives: Drug: Plerixafor
GanetespibExperimentalNot described
Receives: Drug: Ganetespib

What is being measured

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

  1. Response (CR, CRi, PR) achievement, and reasons for failure

    Measured: Duration of treatment

  2. Mortality

    Measured: At 30 days and 8 weeks

  3. Toxicity (haematological and non-haematological)

    Measured: Duration of trial treatment

  4. Survival

    Measured: At 6 and 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 posted8 Nov 2010 (estimated)
  2. Study startApr 2011
  3. Primary completionDec 2013
  4. Study completionJan 2014

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
113 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01236144
Sponsor's protocol ID
SPON 845-10
Other IDs
2010-021444-18, 10/MRE09/27
Acronym
AML18 Pilot
Status last verified
Jun 2014
First submitted
5 Nov 2010
Last updated
11 Jun 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Plerixafor, AC220 and Ganetespib in people with Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome, run by Cardiff University at 13 sites in United Kingdom.

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 8 inclusion and 19 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 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United Kingdom. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Response (CR, CRi, PR) achievement, and reasons for failure (time frame: Duration of treatment). The study lists 4 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 NCT01236144.

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 Jun 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in