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AzTrials

Acute Myeloid LeukemiaPhase 1NCT01636609

Tosedostat and Cytarabine or Azacitidine in Treating Older Participants With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

A Phase 1 study testing Azacitidine, Cytarabine and Tosedostat in people with Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

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

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of cytarabine and azacitidine and how well they work when giving together with tosedostat in treating older participants with acute myeloid leukemia or high risk myelodysplastic syndrome. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Azacitidine, Cytarabine and Tosedostat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
20 Nov 2012to 4 Jul 2019
Phase
Phase 1
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

  • Signed, informed consent must be obtained prior to any study specific procedures
  • For the phase I portion of the study patients should have failed any number of prior therapies, which should include at least the following:
  • Patients with MDS should have failed prior therapy with a hypomethylating agent and/or with lenalidomide
  • Patients with AML should have failed any prior induction therapy or have relapsed after prior therapy
  • Patients with MDS who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for AML
  • Patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive standard therapy or if they refuse standard chemotherapy
Show all 16Show fewer
  • For the phase II portion of the study, only patients who are previously untreated for AML. 1. Patients with history of MDS who received therapy for MDS and progressed to AML are eligible at the time of diagnosis of AML. Only induction chemotherapy administered for AML will be considered for considerations of eligibility regarding prior therapy. Patients who received therapy for MDS before transforming to AML (e.g., with hypomethylating agents or lenalidomide) are eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) while on study and must continue to do so for 3 months after stopping study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study. Pregnant and nursing patients are excluded because the effects of tosedostat on a fetus or nursing child are unknown
  • Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the toxic effects of that therapy to at least grade 1. Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy
  • Serum creatinine =< 2.0 mg/dl
  • Total bilirubin =< 1.5 x the upper limit of normal unless considered due to Gilbert's syndrome
  • Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) =< 3 x the upper limit of normal
  • Left ventricular ejection fraction (LVEF) >= 50% within 28 days prior to first dose of study drug administration
  • Patient is able to comply with all study procedures including study drug administration, visits and tests
  • For patients with history of anthracycline exposure or coronary artery disease co-management by cardiology to optimize cardioprotective medications will be required prior to tosedostat initiation

Who cannot join

  • Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (New York Heart Association class III or IV), or psychiatric illness/social situations that would limit compliance with study requirements
  • Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, clinically significant arrhythmias not controlled by medication, atrial fibrillation (whether active or known past history), uncontrolled angina, or uncontrolled congestive heart failure (New York Heart Association class III or IV)
  • Recent exposure to cardiotoxic agents (including anthracyclines) within 3 months of enrollment. Subjects with troponin-I and brain natriuretic peptide (BNP) levels above upper limit of normal (ULN) are excluded
  • Patients with acute promyelocytic leukemia (APL) (FAB type M3) or chronic myelogenous leukemia (CML) in blast crisis
  • Significant gastrointestinal disorders that may interfere with absorption of tosedostat
  • Patients who have received a stem cell transplant in the past
  • Patients who can receive an allogeneic stem cell transplant within 4 weeks
  • Use of concomitant drugs that prolong QT/corrected QT (QTc) interval are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient, but only if clinically indicated and must be fully documented

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Study of Cytarabine or 5-Azacitidine Combined With Tosedostat to Evaluate the Safety and Tolerability in Older Patients With Acute Myeloid Leukemia (AML) or High Risk MDS

This phase I/II trial studies the side effects and best dose of cytarabine and azacitidine and how well they work when giving together with tosedostat in treating older participants with acute myeloid leukemia or high risk myelodysplastic syndrome. Tosedostat and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tosedostat and cytarabine or azacitidine may work better in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety profile of tosedostat (oral) in combination with cytarabine (subcutaneous [SQ]) or azacitidine (5-azacytidine) in patients age 60 years or older with relapsed/refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

II. To observe the anti-tumor effects of tosedostat in combination with cytarabine or 5-azacytidine, if any occur.

OUTLINE: This is a phase I, dose-escalation of cytarabine and azacitidine followed by a phase II study. Participants are assigned to 1 of 2 arms.

ARM I: Participants receive tosedostat orally (PO) once daily (QD) on days 1-28 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive tosedostat PO QD on days 1-28 and azacitidine intravenously (IV) over 10-40 minutes or SC for on days 1-7. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants will be followed up at 28 days and then every 3-5 months thereafter.

Being tested
Azacitidine, Cytarabine, Tosedostat
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given IV or SC

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given SC

  • TosedostatDrug

    Also called Aminopeptidase inhibitor CHR-2797, CHR-2797

    Given PO

Study groups in NCT01636609
Study groupRoleWhat they receive
Arm I (tosedostat, cytarabine)ExperimentalParticipants receive tosedostat PO QD on days 1-28 and cytarabine SC BID on days 1-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cytarabine; Drug: Tosedostat
Arm II (tosedostat, azacitidine)ExperimentalParticipants receive tosedostat PO QD on days 1-28 and azacitidine IV over 10-40 minutes or SC on days 1-7. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Azacitidine; Drug: Tosedostat

What is being measured

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

  1. Maximum tolerated dose of cytarabine and azacitidine (Phase I)

    Measured: Up to 28 days

  2. Overall response defined as complete response (CR), CR with incomplete platelet recovery (CRp) or CR with insufficient hematological recovery (CRi), morphologic leukemia free state (MLF), partial response (PR), or hematologic improvement (HI)

    Measured: Up to 6 years

Timeline

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

  1. First posted10 Jul 2012 (estimated)
  2. Study start20 Nov 2012
  3. Primary completion4 Jul 2019
  4. Study completion4 Jul 2019

Why it stopped: In 2013 the FDA put a temporary hold on the trial and the Phase II portion of this study was cancelled.

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01636609
Sponsor's protocol ID
2011-0188
Other IDs
NCI-2018-01817, 2011-0188, P30CA016672
Status last verified
Apr 2020
First submitted
6 Jul 2012
Last updated
13 Apr 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine, Cytarabine and Tosedostat in people with Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center 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 16 inclusion and 8 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 13 Apr 2020. 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 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?

The study was stopped early (reason given: In 2013 the FDA put a temporary hold on the trial and the Phase II portion of this study was cancelled.). Results are not available in the source record.

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?

Maximum tolerated dose of cytarabine and azacitidine (Phase I) (time frame: Up to 28 days). The study lists 2 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 NCT01636609.

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 13 Apr 2020.

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