Clinical Trials /

Study of Regorafenib in Patients With Advanced Myeloid Malignancies



This research study is studying a drug as a possible treatment for advanced myeloid malignancies including AML (acute myeloid leukemia), MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplasms) The intervention involved in this study is: -Regorafenib (Stivarga)

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting


Phase 1

Trial Eligibility



  • Brief Title: Study of Regorafenib in Patients With Advanced Myeloid Malignancies
  • Official Title: Phase I Study of Regorafenib in Patients With Advanced Myeloid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 16-464
  • NCT ID: NCT03042689


  • Acute Myeloid Leukemia




This research study is studying a drug as a possible treatment for advanced myeloid malignancies including AML (acute myeloid leukemia), MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplasms) The intervention involved in this study is: -Regorafenib (Stivarga)

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      drug and also tries to define the appropriate dose of the investigational drug to use for
      further studies. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved Regorafenib for this
      specific disease but it has been approved for other uses.

      In this research study, the investigators are looking for the best dose of Regorafenib to
      treat the participant's disease with. Researchers will also look at how effective the study
      drug is in treating the participant's disease and if any side effects occur.

Trial Arms

  • Regorafenib

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of relapsed/refractory advanced malignancies. Specifically: relapsed
             refractory refractory acute myeloid leukemia that have failed one line of prior
             therapy, myelodysplastic syndrome that have failed hypomethylating agents,
             myelofibrosis that have failed ruxolitinib or are ineligible for this therapy.

          -  18 years of age or greater.

          -  ECOG performance status of 0-1.

          -  Able to provide informed consent.

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the ICF until at least 2 months 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.

          -  Able to swallow and retain oral medication.

          -  Normal organ and marrow function defined as:

               -  Total bilirubin ≤ 1.5 x the upper limits of normal (ULN) except for patients with
                  Gilbert's disease.

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
                  (≤ 5 x ULN for subjects with liver involvement of their cancer).

               -  Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver or bone
                  involvement of their cancer).

               -  Serum creatinine ≤ 1.5 x the ULN.

               -  International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x
                  ULN. (Subjects who are prophylactically treated with an agent such as warfarin or
                  heparin will be allowed to participate provided that no prior evidence of
                  underlying abnormality in coagulation parameters exists.)

        Exclusion Criteria:

          -  Previous assignment to treatment during this study. Subjects permanently withdrawn
             from study participation will not be allowed to re-enter the study.

          -  Systemic antineoplastic therapy in the past 14 days (excluding hydroxyurea).

          -  Uncontrolled hypertension (systolic pressure >140 mmHg or diastolic pressure > 90 mmHg
             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.

               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or

               -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
                  before randomization, or myocardial infarction within 6 months before

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Eligible for, have a suitable donor and are willing to undergo Hematopoietic Stem Cell
             Transplantation (HSCT)

          -  Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of
             study medication.

          -  Thrombotic, embolic, venous or arterial events, such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 6 months of informed consent.

          -  Previously untreated or concurrent cancer that is distinct in primary site or
             histology except cervical cancer in-situ, treated ductal carcinoma in situ of the
             breast, curatively treated non-melanoma skin carcinoma, noninvasive aerodigestive
             neoplasms or superficial bladder tumor. Subjects surviving a cancer that was
             curatively treated and without evidence of disease for more than 3 years before
             registration are allowed. All cancer treatments must be completed at least 3 years
             prior to registration.

          -  Known history of human immunodeficiency virus (HIV) infection or current chronic or
             active hepatitis B or C infection requiring treatment with antiviral therapy.

          -  Presence of a non-healing wound, non-healing ulcer or bone fracture.

          -  Major surgical procedure or significant traumatic injury within 28 days before start
             of study medication.

          -  Renal failure requiring hemo-or peritoneal dialysis.

          -  Seizure disorder requiring medication.

          -  Persistent proteinuria ≥ Grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine
             protein: creatinine ratio on a random urine sample).

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed

          -  Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version
             4.0 Grade 2 dyspnea).

          -  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, or intend to become pregnant during the
             study. 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.

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results.

          -  Presence of unresolved toxicities from prior anticancer therapy, defined as having not
             resolved to NCI CTCAE v4.03 grade 0 or 1 with the exception of alopecia. Subjects with
             irreversible toxicity that is not reasonably expected to be exacerbated by regorafenib
             (e.g. hearing loss, neuropathy) may be included after consultation with the principal

          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of regorafenib in patients with advanced myeloid malignancies
Time Frame:2 years
Safety Issue:
Description:To determine the maximum tolerated dose regorafenib in patients with advanced myeloid malignancies.

Secondary Outcome Measures

Measure:Pharmacodynamic effects of regorafenib on cell signaling pathways
Time Frame:2 years
Safety Issue:
Description:To assess pharmacodynamic effect of regorafenib on cell signaling pathways such as FLT-3, RAS and other specific mutations found in each patient's leukemia.
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Measure:To Measure Changes In Specific Markers Of Allele Burden
Time Frame:2 years
Safety Issue:
Description:Measure changes in allele burden with regorafenib treatment using next generation sequencing.


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • AML

Last Updated

September 9, 2020