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Acute Myeloid Leukemia With FLT3/ITD MutationPhase 1NCT01578109

Sorafenib Tosylate Before and After Donor Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia

A Phase 1 study testing Bone Marrow Transplantation, Sorafenib and Sorafenib Tosylate in people with Acute Myeloid Leukemia With FLT3/ITD Mutation, run by National Cancer Institute (NCI) at 2 sites 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

This pilot clinical trial studies the side effects of sorafenib tosylate before and after donor bone marrow transplantation in treating patients with acute myeloid leukemia. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bone Marrow Transplantation, Sorafenib and Sorafenib Tosylate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
2 sitesUnited States
Study dates
13 Jan 2012to 7 Mar 2021
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute myeloid leukemia with a FLT3-internal tandem duplication (ITD) who are in a complete remission or partial remission (less than 10% blasts in marrow) as documented by bone marrow biopsy and who plan to undergo a bone marrow transplantation
  • Patients who have had count recovery (absolute neutrophil count [ANC] > 500,000/mm^3; non transfused platelet count over 30,000/mm^3) and are at least 30 days after induction and/or transplantation but no more than 120 days post transplant
  • Patients may have received any prior therapy deemed necessary for induction of remission except for patients whom have progressed while on sorafenib; patients who have responded to sorafenib previously are eligible for enrollment on the protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than four months
  • Total bilirubin less than 2 x upper limit of normal
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  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal
  • Creatinine =< 1.5 x upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x upper limit of normal
  • The effects of sorafenib on the developing human fetus are unknown; for this reason and because tyrosine kinase inhibiting agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; contraception should continue for at least 30 days after the last dose of sorafenib
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 2 weeks except for intrathecal chemotherapy (i.e., methotrexate, cytarabine, or thiotepa)
  • Patients may not be receiving any other investigational agents
  • Patients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
  • Patients with active and/or untreated central nervous system (CNS) leukemia will not be eligible
  • Patients must not have any evidence of bleeding diathesis or be on any therapeutic anticoagulation such as low molecular weight (LMW) heparin or warfarin for deep vein thrombosis (DVT) treatment
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  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because sorafenib is chemotherapeutic agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued if the mother is treated sorafenib
  • Human immunodeficiency virus (HIV)-positive patients are excluded because management of these patients in the hematopoietic cell transplant setting has not yet been well defined and is currently the subject of investigation in other studies addressing this issue
  • Patients with active acute GVHD who have been initiated on therapy or had therapy escalation within 21 days are not eligible
  • Patients with lack of engraftment (less than 90% donor deoxyribonucleic acid [DNA] in bone marrow or peripheral blood) after bone marrow transplant as evidence by RFLP (restriction fragment length polymorphism) are not eligible
  • Patients who are unable to swallow pills are not eligible
  • Patients taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors including enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, grape fruit juice, or St. John's wort are not eligible

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: A Pilot Study of Sorafenib in Patients With Acute Myeloid Leukemia as Peri-Transplant Remission Maintenance

This pilot clinical trial studies the side effects of sorafenib tosylate before and after donor bone marrow transplantation in treating patients with acute myeloid leukemia. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the toxicity and safety of incorporation of sorafenib tosylate (sorafenib) into the pre- or post-transplant maintenance setting for three types of transplants.

SECONDARY OBJECTIVES:

  1. Improvement of 2 year disease free survival after bone marrow transplant by 25% based on a baseline relapse free survival at two years of 30%.

II. Secondary graft failure is defined as the decline in neutrophil count to < 500/cu mm after achieving engraftment which is unrelated to infection or drug effect (sorafenib?) and is unresponsive to stimulation by growth factors.

III. Non-relapse mortality (NRM) is defined, as death in the absence of competing risks, relapse or progression of disease.

IV. Survival without relapse or death (disease-free survival [DFS]) or without death (overall survival [OS]) will be determined and presented as Kaplan-Meier estimates at 1 and 2 years post-transplant.

  1. Patients will be evaluated for chronic graft versus host disease (GVHD) both as described in the National Institutes of Health (NIH) consensus project guidelines and by conventional criteria.

LABORATORY CORRELATIVE OBJECTIVE:

  1. Patients will undergo serial examinations of bone marrow during the maintenance treatments evaluating minimal residual disease (MRD) by flow cytometry and FLT3 suppression by western blot analysis and plasma inhibitory assay (PIA).

OUTLINE: This is a dose-escalation study.

Patients receive sorafenib tosylate orally (PO) twice daily (BID) beginning at least 30 days after completion of induction therapy and/or transplant but no more than 120 days after transplant continuing for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 24 months.

Being tested
Bone Marrow Transplantation, Sorafenib, Sorafenib Tosylate

What participants receive

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

  • Bone Marrow TransplantationProcedure or surgery

    Also called Blood and Bone Marrow Transplant, BMT, Bone Marrow Grafting, Bone Marrow Transplant

    Undergo BMT

  • SorafenibDrug

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

    Given PO

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

    Given PO

Study groups in NCT01578109
Study groupRoleWhat they receive
Treatment (sorafenib tosylate and transplant)ExperimentalPatients receive sorafenib tosylate PO BID beginning at least 30 days after completion of induction therapy and/or transplant and no more than 120 days after transplant continuing for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Bone Marrow Transplantation; Drug: Sorafenib; Drug: Sorafenib Tosylate

What is being measured

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

  1. Proportion of patients removed from the study in each cohort due to toxicity

    Will be reported with exact binomial proportions and 95% confidence intervals. All toxicities by type and grade will be reported. The proportion of patients with graft failure in each cohort will also be reported with exact binomial proportions and 95% confidence intervals.

    Measured: Up to 24 months

Secondary outcomes (6)

  1. Cumulative incidence of non-relapse mortality and relapse

    Estimated by competing risks analysis using Grey's method.

    Measured: Up to 2 years

  2. Disease-free survival (DFS)

    Standard life table methods with Kaplan-Meier (KM) plots will be used to analyze DFS. Reported with 90% confidence intervals overall and by cohort.

    Measured: Up to 2 years

  3. Overall survival (OS)

    Standard life table methods with KM plots will be used to analyze OS. Reported with 90% confidence intervals overall and by cohort.

    Measured: Up to 2 years

  4. Change in minimal residual disease (MRD)

    Will be assessed by flow cytometry. Box plots will be used.

    Measured: Baseline to day 365

  5. Change in FLT3 suppression

    Will be assessed by plasma inhibitory assay and western blotting. Box plots will be used.

    Measured: Baseline to day 365

  6. Pharmacodynamic parameters of sorafenib tosylate

    Samples will be collected to assess sorafenib tosylate and the N-oxide metabolite (total and unbound) exposure to correlate with pharmacodynamic endpoints using non-parametric statistics.

    Measured: Up to 2 years post-transplant

Timeline

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

  1. First posted16 Apr 2012 (estimated)
  2. Study start13 Jan 2012
  3. Primary completion28 Oct 2020
  4. Study completion7 Mar 2021

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01578109
Sponsor's protocol ID
NCI-2012-00727
Other IDs
NCI-2012-00727, J11116, CDR0000730684, 8992, 8992, P01CA015396, P30CA006973, P50CA100632
Status last verified
Apr 2024
First submitted
13 Apr 2012
Last updated
2 Apr 2024
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bone Marrow Transplantation, Sorafenib and Sorafenib Tosylate in people with Acute Myeloid Leukemia With FLT3/ITD Mutation, run by National Cancer Institute (NCI) at 2 sites 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 13 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 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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?

Proportion of patients removed from the study in each cohort due to toxicity (time frame: Up to 24 months). 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 NCT01578109.

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 2 Apr 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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