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Recurrent Acute Myeloid LeukemiaPhase 1/2NCT03247088

Sorafenib, Busulfan and Fludarabine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia Undergoing Donor Stem Cell Transplant

A Phase 1/2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I/II trial studies the best dose of sorafenib when given together with busulfan and fludarabine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment and who are undergoing donor stem cell transplant. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
74 participants
Where
1 siteUnited States
Study dates
30 Jul 2017to 31 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 and =< 70 years
  • Patients with acute myeloid leukemia both flt3 positive and negative
  • Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor available
  • Life expectancy of at least 12 weeks (3 months)
  • Direct bilirubin =< 1 mg/dL
  • Alanine transaminase (ALT) =< 3 x upper limit of normal
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  • Serum creatinine =< 1.5 x the upper limit of normal
  • Creatinine clearance >= 50
  • Diffusing capacity for carbon monoxide (DLCO) > 50% of predicted corrected for hemoglobin
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
  • Subject must be able to swallow and retain oral medication

Who cannot join

  • Acute myeloid leukemia in first complete molecular remission and favorable risk disease as defined by presence of t(8:21) or inv (16)
  • Patients with a comorbidity score > 3. The principal investigator is the final arbiter of eligibility for comorbidity score > 3
  • Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0] on repeated measurement) despite optimal medical management
  • Active or clinically significant cardiac disease including:
  • Congestive heart failure - New York Heart Association (NYHA) > class II
  • Active coronary artery disease
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  • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
  • Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
  • Evidence or history of bleeding diathesis or coagulopathy. Patients with bleeding due to prior thrombocytopenia are permitted
  • Subject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v. 4.0 grade 2 or higher within 4 weeks before randomization; any other hemorrhage/bleeding event of NCI-CTCAE v. 4.0 grade 3 or higher within 4 weeks before randomization
  • Subjects with thrombotic, embolic, venous, or arterial cerebrovascular event (including transient ischemic attacks) within 6 months of informed consent
  • Subjects who have used strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, St. John's wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before randomization
  • Subjects with any previously untreated or concurrent cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form)
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • History of organ allograft (including corneal transplant)
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
  • Any malabsorption condition
  • Women who are pregnant or breast-feeding
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments
  • Any medical, psychological, or psychosocial condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
  • Major surgery within 30 days prior to start of study drug
  • Patients who received inotuzumab and/or gemtuzumab in the past
  • Therapeutic anticoagulation with vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids
  • However, prophylactic anticoagulation as described below is allowed:
  • Low dose warfarin (1 mg orally, once daily) with prothrombin time international normalized ratio (PT-INR). =< 1.5 x upper limit of normal (ULN) is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on sorafenib or capecitabine therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes
  • Low dose aspirin (=< 100 mg daily)
  • Prophylactic doses of heparin or low molecular weight heparin

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 Sorafenib Added to Busulfan and Fludarabine Conditioning Regimen in Patients With Relapsed/Refractory AML Undergoing Stem Cell Transplantation

This phase I/II trial studies the best dose of sorafenib when given together with busulfan and fludarabine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment and who are undergoing donor stem cell transplant. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as busulfan and fludarabine, 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. Giving sorafenib with busulfan and fludarabine may work better in treating patients with recurrent or refractory acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To identify the maximum tolerated dose (MTD) of sorafenib when combined with busulfan and fludarabine conditioning regimen.

II. To obtain preliminary evidence of efficacy.

SECONDARY OBJECTIVES:

  1. To determine safety of this regimen as per National Cancer Institute (NCI) toxicity criteria.

II. To determine time to neutrophil and platelet engraftment. III. To determine incidence of acute and chronic graft versus host disease (GVHD).

IV. To determine relapse incidence. V. To determine non relapse mortality. VI. To determine overall survival.

TERTIARY OBJECTIVES:

  1. To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To study immune recovery and cytokines (both in plasma and cells).

OUTLINE: This is a phase I, dose escalation study of sorafenib, followed by a phase II study.

PRE-STEM CELL INFUSION: Patients receive sorafenib orally (PO) once daily (QD) or twice daily (BID) on days -24 to -5, busulfan intravenously (IV) over 3 hours on days -20 and -13 and -6 and -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.

STEM CELL INFUSION: Patients receive allogeneic hematopoietic stem cell transplant (HSCT) IV in the absence of disease progression or unacceptable toxicity.

POST-STEM CELL INFUSION: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus PO BID beginning day 5 for about 50 days, filgrastim subcutaneously (SC) on day 7 and sorafenib PO BID beginning between days +30 and +120 for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with matched unrelated donor receive mycophenolate mofetil PO thrice daily (TID) or IV over 2 hours TID beginning on day 5 for up to 90 days for longer.

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.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC

    Undergo allogeneic HSCT IV

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FilgrastimBiological

    Also called Filgrastim-aafi, G-CSF, Neupogen, Nivestym

    Given SC

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Mycophenolate MofetilDrug

    Also called CellCept, MMF

    Given PO

  • SorafenibDrug

    Also called BA4 43 9006, BAY 43-9006, Bay-439006

    Given PO

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given PO

Study groups in NCT03247088
Study groupRoleWhat they receive
Treatment (sorafenib, busulfan, fludarabine, HSCT)ExperimentalPRE-STEM CELL INFUSION: Patients receive sorafenib orally PO QD or BID on days -24 to -5, busulfan IV over 3 hours on days -20 and -13 and -6 and -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity. STEM CELL INFUSION: Patients receive allogeneic HSCT IV in the absence of disease progression or unacceptable toxicity. POST-STEM CELL INFUSION: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus PO BID beginning day 5 for about 50 days, filgrastim SC on day 7 and sorafenib PO BID beginning between days +30 and +120 for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with matched unrelated donor receive mycophenolate mofetil PO TID or IV over 2 hours TID beginning on day 5 for up to 90 days for longer.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Drug: Sorafenib; Drug: Tacrolimus

What is being measured

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

  1. Maximum tolerated dose (MTD) as defined by toxicity (Phase I)

    Toxicity is defined as grade 3 or higher regimen-related non-hematologic, non-infectious, and non-graft versus host disease (GVHD) toxicity occurring during the period from day -5 to pre-transplant to day 30 post-transplant. Dose-finding will be done using the Bayesian Model Averaging Continual Reassessment (BMA-CRM) method.

    Measured: From day -24 pre-transplant to day 30 post-transplant

  2. Progression-free survival (PFS) (Phase II)

    The method of Thall et al will be used to monitor PFS time. PFS will be estimated using the method of Kaplan and Meier. The relationship between patient prognostic covariates and PFS and overall survival (OS) time will be assessed by Bayesian survival time regression.

    Measured: Interval between day of transplant and day of death or disease progression, assessed up to 6 years

Secondary outcomes (6)

  1. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 6 years

  2. OS

    OS will be estimated using the method of Kaplan and Meier. Categorical variables will be tabulated. The relationship between patient prognostic covariates and PFS and OS time will be assessed by Bayesian survival time regression.

    Measured: Interval between day of transplant and day of death, assessed up to 6 years

  3. Non-relapse mortality rate

    Defined as death from any cause other than relapse disease. These events will be tabulated.

    Measured: Up to 6 years

  4. Relapse rate

    These events will be tabulated.

    Measured: Up to 6 years

  5. Graft failure

    These events will be tabulated.

    Measured: Up to 6 years

  6. Incidence of acute and chronic graft versus host disease graded according to National Cancer Institute CTCAE version 4.0

    These events will be tabulated.

    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 posted11 Aug 2017
  2. Study start30 Jul 2017
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

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
74 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03247088
Sponsor's protocol ID
2016-0592
Other IDs
NCI-2018-01607, 2016-0592
Status last verified
Jun 2026
First submitted
8 Aug 2017
Last updated
10 Jun 2026
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 1/2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cyclophosphamide in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid 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 14 inclusion and 27 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: under way, not looking for participants, as of the sponsor's last update on 10 Jun 2026. 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 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?

This study is still under way. Results are not available in the source record yet.

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 (MTD) as defined by toxicity (Phase I) (time frame: From day -24 pre-transplant to day 30 post-transplant). 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 NCT03247088.

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 10 Jun 2026.

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