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LeukemiaPhase 2NCT02196857

Sorafenib Plus 5-Azacitidine Initial Therapy of Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MS) With FLT3-ITD Mutation

A Phase 2 study testing Azacytidine and Sorafenib in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

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

Official record
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Trial summary

The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can help to control the disease in patients with Acute Myeloid Leukemia (AML) and high risk Myelodisplastic Syndrome (MDS) with FLT3-ITD mutation. The safety of this drug combination will also be studied. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Azacytidine and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
6 Feb 2015to 27 Nov 2018
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with untreated AML (> or equal to 20% blasts in bone marrow and/or peripheral blood) or high risk MDS (> or equal to 10% blasts in bone marrow). A. Patients with AML and history of MDS who have received prior therapy with a hypomethylating agent (including azacytidine) and/or with lenalidomide for prior MDS are eligible if the treating physician feels that participation in the study is in the patients' best interest. B. Patients should have molecular evidence of the presence of FLT3-ITD mutation with a molecular burden of at least 10%.
  • Age > or equal to 60 years; patients younger than 60 who are unsuitable for or unwilling to receive standard cytotoxic chemotherapy are also eligible to be enrolled.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status < or equal 2.
  • Adequate liver (bilirubin < or equal to 1.5 x ULN, Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) < or equal to 2.5 x ULN and Alkaline phosphatase < or equal to 4 x ULN if not related to leukemic disease) and renal (creatinine < or equal to 1.5 x ULN) function.
  • Patients must provide written informed consent.
  • Patients must have been off therapy for MDS for 2 weeks prior to entering this study, and must have recovered from the toxic effects of that therapy to at least grade 1, unless there is evidence of rapidly progressive disease. Use of hydroxyurea (any dose) or ara-C (up to 1 g/m^2 X 2 doses) for patients with rapidly proliferative disease is allowed before the start of study therapy; these should be stopped for 24 hours prior to the initiation of azacitidine and sorafenib.
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  • Women of childbearing potential should be advised to avoid becoming pregnant with an adequate method of contraception (barrier or hormonal methods) and men should be advised to not father a child while receiving treatment with azacitidine. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below: Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Men should use adequate birth control for at least 30 days after the last administration of sorafenib. Post-menopausal women (defined as no menses for at least one year) and surgically sterilized women are not required to undergo a pregnancy test. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study.
  • 7. Continued: Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study.
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
  • International Normalized Ratio (INR) < or equal to 1.5. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored weekly, or as defined by the local standard of care, until INR is stable.

Who cannot join

  • Nursing and pregnant females.
  • Patients with acute promyelocytic leukemia are excluded.
  • Patients with known allergy to sorafenib or azacitidine, mannitol or any of their components.
  • Patients with known severe impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sorafenib.
  • Patients with any other known disease (except carcinoma in-situ) or concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and uncontrolled hypertension, chronic renal disease (creatinine clearance < 20 ml/min using the Cockcroft and Gault formula), or active uncontrolled infection) which could compromise participation in the study.
  • Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis (B or C).
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  • Patients who have had any major surgical procedure within 28 days prior to Day 1.
  • Patients unwilling or unable to comply with the protocol.
  • Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Uncontrolled hypertension defined as systolic blood pressure > 150? mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Active clinically serious infection > CTCAE v4, Grade 2 not controlled with antibiotics.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > or equal to CTCAE v4. Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > or equal to CTCAE v4. Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence of bleeding diathesis or coagulopathy within the past 6 months.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results including known non-compliance issues on study trials.
  • Use of strong CYP3A4 inducer.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Sorafenib Plus 5-Azacitidine for the Initial Therapy of Patients With Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome With FLT3-ITD Mutation

The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can help to control the disease in patients with Acute Myeloid Leukemia (AML) and high risk Myelodisplastic Syndrome (MDS) with FLT3-ITD mutation. The safety of this drug combination will also be studied.

Read the detailed description

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive 5-azacitidine either as an injection under the skin or by vein on Days 1-7 of each 28-day cycle. If by vein, the infusion will take about 10-40 minutes.

You will take sorafenib by mouth 2 times a day about 12 hours apart, with at least 1 cup (8 ounces) of water on an empty stomach, every day. If you vomit a dose, do not make it up. You should wait and take your next scheduled dose.

Each study cycle may last a little longer than 28 days, depending on how you are doing.

Study Visits:

Each week, blood (about 1 tablespoon) will be drawn for routine tests.

Each week for the first 6 weeks, and then as often as your doctor thinks it is needed, you will have your blood pressure measured.

Before each cycle, you will have a physical exam.

Before every 2-4 cycles, you will have a bone marrow aspirate to check the status of the disease.

Length of Study:

You may continue taking the study drugs for as long as your doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Study Visit:

After you have stopped taking the study drugs, the following tests and procedures will be performed:

  • You will have a physical exam.
  • You will have a bone marrow aspirate to check the status of disease.
  • Blood (about 2 tablespoons) will be drawn for routine tests.

Follow-Up Visits:

After your end-of-study visit, you will return to the clinic every 3 months and have the following tests and procedures:

  • You will have a physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests.

This is an investigational study. Sorafenib is FDA approved and commercially available for the treatment of kidney cancer and liver cancer. 5-azacitidine is FDA approved for the treatment of MDS, but combining it with sorafenib is investigational. The study doctor can tell you how the study drugs are designed to work.

Up to 52 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions
Leukemia
Being tested
Azacytidine, Sorafenib
Keywords
Leukemia, Acute myeloid leukemia, AML, High risk myelodysplastic syndrome, MDS, FLT3-ITD mutation, Azacytidine, 5-Azacytidine, 5-AZA, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Sorafenib, Nexavar, BAY 43-9006
Medical subject headings
Leukemia, Leukemia, Myeloid, Acute

What participants receive

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

  • AzacytidineDrug

    Also called 5-Azacytidine, 5-AZA, Vidaza, 5-AZC

    75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.

  • SorafenibDrug

    Also called Nexavar, BAY 43-9006

    400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.

Study groups in NCT02196857
Study groupRoleWhat they receive
Azacytidine + SorafenibExperimentalAzacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Receives: Drug: Azacytidine; Drug: Sorafenib

What is being measured

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

  1. Participants With a Response CR + PR + CRi

    Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as </= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.

    Measured: After 3, 28 day cycles

Secondary outcomes (1)

  1. Toxicity Profile of Azacytidine and Sorafenib

    Severity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.

    Measured: After 3, 28 day cycles

Timeline

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

  1. First posted22 Jul 2014 (estimated)
  2. Study start6 Feb 2015
  3. Primary completion27 Nov 2018
  4. Study completion27 Nov 2018

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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02196857
Sponsor's protocol ID
2014-0076
Other IDs
NCI-2014-01702
Status last verified
Jan 2020
First submitted
18 Jul 2014
Last updated
14 Jan 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ohanian M, Garcia-Manero G, Levis M, Jabbour E, Daver N, Borthakur G, Kadia T, Pierce S, Burger J, Richie MA, Patel K, Andreeff M, Estrov Z, Cortes J, Kantarjian H, Ravandi F. Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia. Am J Hematol. 2018 Sep;93(9):1136-1141. doi: 10.1002/ajh.25198. Epub 2018 Aug 31.

    PubMed 30028037

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacytidine and Sorafenib in people with Leukemia, 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 10 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 14 Jan 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 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 6 Jan 2020). 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?

Participants With a Response CR + PR + CRi (time frame: After 3, 28 day cycles). 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 NCT02196857, 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 14 Jan 2020.

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