AzTrials
AzTrials

LeukemiaPhase 1/2NCT00516828

Sorafenib and Low Dose Cytarabine in Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

A Phase 1/2 study testing cytarabine in people with Leukemia and Myelodysplastic Syndromes, run by NCIC Clinical Trials Group at 4 sites in Canada.

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

RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from… Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Leukemia, Myelodysplastic Syndromes
What is being tested?
cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesCanada
Study dates
27 Nov 2007to 10 Jan 2013
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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:
  • Acute myeloid leukemia (AML) by FAB criteria (By morphology and routine histochemistry and confirmed, when possible, by flow cytometric analysis of surface immunophenotype; co-expression of lymphoid markers permitted)
  • High-risk myelodysplastic syndromes defined as IPSS category of intermediate-2 or greater
  • Must be considered unsuitable for intensive chemotherapy regimens
  • No documented CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • AST and ALT ≤ 2 times upper limit of normal (ULN)
  • Bilirubin normal
  • Creatinine ≤ 1.2 times ULN OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ carcinoma of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • No upper gastrointestinal or other conditions that would preclude compliance with or administration of oral medication
  • No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including any of the following:
  • History of significant neurologic or psychiatric disorder that would impair the ability to obtain consent
  • Active, uncontrolled, serious infections
  • Active peptic ulcer disease
  • Evidence of bleeding diathesis
  • No myocardial infarction within the past 6 months
  • No congestive heart failure
  • No unstable angina
  • No active cardiomyopathy or unstable ventricular arrhythmia
  • No poorly controlled hypertension (e.g., systolic BP ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg)
  • No known hypersensitivity to the study drugs or their components
  • No preexisting hypothyroidism prior to enrollment unless patient is euthyroid on medication
  • No neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

  • At least 2 days since prior hydroxyurea
  • No other prior chemotherapy
  • No concurrent therapeutic doses (≥ 2 mg/day) of anticoagulants (e.g., warfarin)
  • Doses of up to 2 mg/day given for prophylaxis of thrombosis are accepted provided INR is ≤ 1.5
  • No other concurrent experimental drugs or anticancer therapy

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • QEII Health Sciences Center

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I/II Study of Sorafenib (BAY 43-9006) in Combination With Low Dose ARA-C (CYTARABINE) in Elderly Patients With AML or High-Risk MDS

RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cytarabine may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving sorafenib together with cytarabine and to see how well it works in treating older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Read the detailed description

OBJECTIVES:

  • To determine the recommended dose of sorafenib tosylate and cytarabine when given in combination to elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndromes who are not suitable for intensive chemotherapy. (Phase I)
  • To determine the safety, tolerability, toxicity profile, and dose-limiting toxicities in patients treated with this regimen. (Phase I)
  • To estimate the efficacy (as measured by complete response rate) in patients treated with this regimen. (Phase II)
  • To describe the toxic effects and overall response rate (complete and partial) in patients treated with this regimen. (Phase II)
  • To evaluate potential correlates of response in translational research studies including FLT-3 internal tandem duplications and point mutations in blasts. (Phase II)

OUTLINE: This is a multicenter study.

  • Phase I: Patients receive oral sorafenib tosylate twice daily on days 2-28 and cytarabine subcutaneously twice daily on days 1-10 at the dose level assigned at registration. Doses of both drugs will be escalated and the recommended doses for the combination will be determined. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who respond to treatment will receive 2 cycles after response criteria are met.
  • Phase II: Patients receive sorafenib tosylate and cytarabine as in phase I at the recommended doses for the combination determined in phase I.

Bone marrow (or blood) samples are collected at baseline and at the end of each course of study treatment. Baseline samples are analyzed for mutational status of FLT-3 (i.e., internal tandem duplication [ITD] and point mutations).

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until progression and toxicities resolve.

Being tested
cytarabine
Keywords
adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), untreated adult acute myeloid leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Congenital Abnormalities

What participants receive

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

  • cytarabineDrug

    subcutaneously twice daily from Day 1 to 10

Study groups in NCT00516828
Study groupRoleWhat they receive
Sorafenib and CytarabineExperimentalCytarabine: subcutaneously twice daily from day 1 - 10. Sorafenib: Days 2-28; at the dose level assigned at registration. Sorafenib will be given orally twice daily.
Receives: Drug: cytarabine

What is being measured

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

  1. Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I)

    Measured: 29 months

  2. Dose-limiting toxicity (Phase I)

    Measured: 29 months

  3. Complete remission (Phase II)

    Measured: 29 months

Secondary outcomes (5)

  1. Overall response rate (complete and partial response) (Phase II)

    Measured: 29 months

  2. Time to progression (Phase II)

    Measured: 29 months

  3. Overall survival (Phase II)

    Measured: 29 months

  4. FLT-3 ITD endpoint mutation response correlation.

    Measured: 29 months

  5. Toxicity (Phase II)

    Measured: 29 months

Timeline

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

  1. First posted15 Aug 2007 (estimated)
  2. Study start27 Nov 2007
  3. Primary completion18 Mar 2010
  4. Study completion10 Jan 2013

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00516828
Sponsor's protocol ID
I186
Other IDs
CAN-NCIC-IND186, CDR0000560975
Status last verified
Apr 2020
First submitted
14 Aug 2007
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Macdonald DA, Assouline SE, Brandwein J, Kamel-Reid S, Eisenhauer EA, Couban S, Caplan S, Foo A, Walsh W, Leber B. A phase I/II study of sorafenib in combination with low dose cytarabine in elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndrome from the National Cancer Institute of Canada Clinical Trials Group: trial IND.186. Leuk Lymphoma. 2013 Apr;54(4):760-6. doi: 10.3109/10428194.2012.737917. Epub 2012 Nov 15.

    PubMed 23061485

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing cytarabine in people with Leukemia and Myelodysplastic Syndromes, run by NCIC Clinical Trials Group at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. 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?

Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I) (time frame: 29 months). 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?

On the ClinicalTrials.gov record for NCT00516828, which also lists 1 linked publication.

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 4 Aug 2023.

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
Clinical Trial NCT00516828 | AzTrials