Clinical Trials /

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

NCT01578109

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Sorafenib Tosylate Before and After Donor Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia
  • Official Title: A Pilot Study of Sorafenib in Patients With Acute Myeloid Leukemia as Peri-transplant Remission Maintenance

Clinical Trial IDs

  • ORG STUDY ID: NCI-2012-00727
  • SECONDARY ID: NCI-2012-00727
  • SECONDARY ID: J11116
  • SECONDARY ID: CDR0000730684
  • SECONDARY ID: 8992
  • SECONDARY ID: 8992
  • SECONDARY ID: P01CA015396
  • SECONDARY ID: P30CA006973
  • SECONDARY ID: P50CA100632
  • SECONDARY ID: U01CA070095
  • SECONDARY ID: UM1CA186691
  • NCT ID: NCT01578109

Conditions

  • Acute Myeloid Leukemia in Remission
  • Acute Myeloid Leukemia With FLT3/ITD Mutation

Interventions

DrugSynonymsArms
Sorafenib TosylateBAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibTreatment (sorafenib tosylate and transplant)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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.

      V. 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.

      TERTIARY OBJECTIVES:

      I. Patients will undergo serial examinations of bone marrow during the maintenance treatments
      evaluating minimal residual disease (MRD) by flow cytometry and fms-related tyrosine kinase 3
      (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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Sorafenib Tosylate

Eligibility Criteria

        Inclusion Criteria:

          -  Acute myeloid leukemia with a fms-like tyrosine kinase 3 (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

          -  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

          -  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

        Exclusion Criteria:

          -  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

          -  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; breastfeeding should be discontinued if
             the mother is treated sorafenib

          -  Human immunodeficiency virus (HIV)-positive patients are excluded

          -  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, carbazepine, or
             phenobarbitol), rifampin, grape fruit juice, or St. John's wort are not eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients removed from the study in each cohort due to toxicity
Time Frame:Up to 24 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Cumulative incidence of NRM and relapse
Time Frame:Up to 2 years
Safety Issue:
Description:Estimated by competing risks analysis using Grey's method.
Measure:DFS
Time Frame:Up to 2 years
Safety Issue:
Description:Standard life table methods with Kaplan-Meier (KM) plots will be used to analyze DFS. Reported with 90% confidence intervals overall and by cohort.
Measure:OS
Time Frame:Up to 2 years
Safety Issue:
Description:Standard life table methods with KM plots will be used to analyze OS. Reported with 90% confidence intervals overall and by cohort.
Measure:Change in MRD by flow cytometry
Time Frame:Baseline to day 365
Safety Issue:
Description:Box plots will be used.
Measure:Change in FLT3 suppression by PIA and western blotting
Time Frame:Baseline to day 365
Safety Issue:
Description:Box plots will be used.
Measure:Pharmacodynamic parameters of sorafenib tosylate
Time Frame:Up to 2 years post-transplant
Safety Issue:
Description: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.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:National Cancer Institute (NCI)

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