AzTrials
AzTrials

Myeloid Leukemia, ChronicPhase 2NCT00114959

Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)

A Phase 2 study testing Homoharringtonine and Imatinib Mesylate in people with Myeloid Leukemia, Chronic and Myeloid Leukemia, Chronic, Accelerated-Phase, run by ChemGenex Pharmaceuticals at 1 site in United States.

Terminated

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

Official record
Search all trials

Trial summary

This will be an open label, multi-center study of up to 77 patients with CML in chronic, accelerated or blast phase who have developed resistance to or have failed previous treatment with Gleevec (imatinib mesylate). Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Homoharringtonine and Imatinib Mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Oct 2005to Mar 2009
Phase
Phase 2
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female patients 16 years or older
  • Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in either chronic, accelerated or blast phase
  • Patients with chronic phase CML will be either refractory (failed to achieve hematologic or cytogenetic response) or resistant (responded initially but subsequently lost hematologic or cytogenetic response) to prior imatinib mesylate therapy. Failure to achieve cytogenetic response is defined as follows: no cytogenetic response after 3 months of therapy with imatinib mesylate, no major cytogenetic response at 12 months of therapy, loss of complete cytogenetic response documented twice, or loss of major cytogenetic response at least once.
  • Patients with accelerated or blast phase may be newly diagnosed and previously untreated or if previously treated with imatinib mesylate, will be refractory or resistant to this agent or have failed to achieve at least a complete hematologic or cytogenetic response to treatment, as previously defined.
  • Patients in accelerated phase will meet one or more of the following criteria: greater than or equal to 15% through less than 30% blasts in peripheral blood or bone marrow, greater than or equal to 30% blasts + promyelocytes in peripheral blood or bone marrow, greater than or equal to 20% basophils in peripheral blood, platelet count less than 100*10^9/L unrelated to therapy or clonal evolution.
  • CML in blast phase will be defined as greater than or equal to 30% blasts in the bone marrow or presence of extramedullary disease
Show all 12Show fewer
  • Patients must have completed all previous anti-leukemic therapy for at least 2 weeks, except as noted, and have fully recovered from side effects of a previous therapy, unless disease progression necessitates early therapy. Patients may receive leukapheresis, hydroxyurea and anagrelide for up to 24 hours prior to start of study treatment. Patients receiving imatinib mesylate may continue to receive it uninterrupted, except for a 3-day window at treatment cycle 1.
  • Bilirubin less than or equal to 2 times the upper limit of normal (ULN); alanine aminotransferase (ALT) less than or equal to 3 times ULN; creatinine less than or equal to 1.5 times ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  • Be able to comply with the requirements of the entire study
  • Be able and willing to provide written informed consent prior to any study related procedure
  • Patients and their partners must use an effective contraceptive during the study dosing period. The following are considered effective contraceptives: oral contraceptive pill, condom, diaphragm plus spermicide, abstinence, patient or partner surgically sterile, patient or partner more than 2 years post-menopausal, or injectable or implantable agent/device.

Who cannot join

  • New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or congestive heart failure
  • Myocardial infarction in the previous 12 weeks
  • Other intercurrent illness which would preclude study conduct and assessment, including but not limited to another active malignancy, uncontrolled and active infection, positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II status
  • Pregnant or lactating
  • Any medical or psychiatric condition which may compromise the ability to give written informed consent or to comply with the study protocol

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Univ. of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Open-Label Study of the Intravenous Administration of Homoharringtonine (CGX-635) Combined With the Oral Administration of Gleevec in the Treatment of Patients With Chronic Myeloid Leukemia (CML) in Chronic, Accelerated, and Blast Phase

This will be an open label, multi-center study of up to 77 patients with CML in chronic, accelerated or blast phase who have developed resistance to or have failed previous treatment with Gleevec (imatinib mesylate). Because these patients may still be sensitive to Gleevec, adding Homoharringtonine may restore a response to Gleevec or the combined treatment may promote a better response than using Gleevec alone.

Read the detailed description

Every 4 weeks, the study medicine Homoharringtonine will be given by vein daily for 5 days along with continuing daily doses of the approved medicine Gleevec taken by mouth. The safety and effectiveness of this combined treatment in CML patients will be studied. Patients who do not achieve a meaningful hematologic or cytogenetic response after 4 cycles or less will be discontinued. Otherwise, patients may continue additional cycles of this combined treatment for a maximum of 12 cycles.

Being tested
Homoharringtonine, Imatinib Mesylate
Keywords
ChemGenex Pharmaceuticals, Ltd, ChemGenex Pharmaceuticals, ChemGenex, Chronic Myeloid Leukemia, Myeloid Leukemia, Chronic, Leukemia, Myeloid Leukemia, Chronic Phase, Accelerated Phase, Blast Phase, Myeloid, Leukemia, Chronic, Accelerated Phase, Myeloid, Leukemia, Chronic, Leukemia, Myeloid, Chronic, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myeloid, Chronic Phase, Leukemia, Myeloid, Accelerated-Phase, Myeloid, Leukemia, Chronic, Chronic Phase, Leukemia, Myeloid, Accelerated Phase, Homoharringtonine, Omacetaxine
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myeloid, Chronic-Phase, Leukemia, Leukemia, Myeloid

What participants receive

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

  • HomoharringtonineDrug

    Also called Omacetaxine mepesuccinate, CGX-635

    Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous (IV) infusion daily on Days 1-5 of each 4 week treatment cycle. Participants who do not achieve a meaningful hematologic or cytogenetic response by the end of the fourth cycle are discontinued from the study. Otherwise, participants may continue additional cycles of this combined treatment for a maximum of 12 cycles.

    Participants who achieved a molecular or cytogenetic response, or a complete hematologic remission (CHR), could undergo subsequent cycles with a maintenance schedule of homoharringtonine 2.5 mg/m^2 by continuous 24-hour IV infusion daily for 2 days every 4 weeks. Dose escalations in subsequent cycles were allowed by one day at a time if the participant was unable to maintain CHR in the maintenance schedule.

  • Imatinib MesylateDrug

    Also called Gleevac

    Taken by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML. For the first cycle of therapy only, imatinib was started on Day 4 of homoharringtonine treatment.

Study groups in NCT00114959
Study groupRoleWhat they receive
Homoharringtonine + Imatinib MesylateExperimentalParticipants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Receives: Drug: Homoharringtonine; Drug: Imatinib Mesylate

What is being measured

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

  1. Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response

    Participants in accelerated or blast phase who converted to at least CML-chronic phase.

    CML in accelerated phase meets one or more of the following criteria: >=15% - <30% blasts in peripheral blood or bone marrow, >=30% blasts + promyelocytes in peripheral blood or bone marrow, >=20% basophils in peripheral blood; platelet count <100*10^9/L unrelated to therapy or clonal evolution. CML in blast phase have >=30% blasts in the bone marrow or presence of extramedullary disease.

    Meaningful responses include (in descending order of health)

    • Complete Hematologic Remission (CHR)
    • Partial Hematologic Remission (PHR)
    • Hematologic Improvement (HI)
    • Partial Response (PR)
    • Return to Chronic Phase (RCP). A return to chronic phase involves the disappearance of blastic phase features and a return to chronic phase CML picture, i.e., peripheral blasts <15%, peripheral blasts and promyelocytes <30%, peripheral basophils <20%, and platelets >100*10^9/L.

    Measured: up to month 4

  2. Proportion of Participants With Chronic Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response

    Participants who are not in complete hematologic remission (CHR) at study start must achieve at least a CHR, and participants who are in CHR at onset must demonstrate an improvement in their cytogenetics.

    A Complete Hematologic Remission (CHR) involves normalization of the bone marrow (less than 5% blasts) and peripheral blood with white blood cells < 10*10^9/L, absolute neutrophil count >=1*10^9/L, platelets >=100*10^9/L and no peripheral blasts, promyelocytes or myelocytes. This is in addition to disappearance of all signs and symptoms of the disease.

    Measured: up to month 4

  3. Number of Participants With Adverse Experiences (AEs)

    Summary of participants who had adverse events (AEs), who discontinued treatment due to the AE, who had serious adverse events (SAEs), and who had SAEs that were related to treatments.

    A serious adverse event is one that at any dose of the study drug or at any time during the period of observation:

    • Results in death;
    • Is life threatening;
    • Requires inpatient hospitalization or prolongation of existing hospitalization;
    • Results in persistent or significant disability/incapacity;
    • Is a congenital anomaly/birth defect;
    • Is medically important.

    The Investigator assessed each AE for potential causal relationship between the event and study drug. An investigator assessment of possibly, probably or unknown relation is considered related.

    Measured: up to 3 years

Secondary outcomes (1)
  1. Participants With Complete Hematologic Remission Suppression of the Philadelphia Chromosome

    Complete hematologic remission was further classified according to the suppression of the Philadelphia chromosome (Ph) as:

    No cytogenetic response - Ph positive 100% Minimal cytogenetic response - Ph positive 35-90% Partial cytogenetic response - Ph positive 1-34% Complete cytogenetic response - Ph positive 0%

    Measured: up to month 4

Timeline

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

  1. First posted21 Jun 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionJun 2008
  4. Study completionMar 2009

Why it stopped: Poor enrollment

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00114959
Sponsor's protocol ID
CGX-635-CML-201
Other IDs
MDACC protocol #2005-0067
Status last verified
Jan 2015
First submitted
20 Jun 2005
Last updated
15 Jan 2015
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Homoharringtonine and Imatinib Mesylate in people with Myeloid Leukemia, Chronic and Myeloid Leukemia, Chronic, Accelerated-Phase, run by ChemGenex Pharmaceuticals at 1 site in United States.

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 12 inclusion and 5 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 15 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 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?

Yes. Results are posted in the registry (first posted 15 Jan 2015). 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?

Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response (time frame: up to month 4). 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?
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 15 Jan 2015.

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