Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome

NCT01254890 | Completed Phase 1 Results

• 2 other identifiers: 2010-0511NCI-2011-00257
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can control the disease in patients with AML or MDS. The safety of this drug combination will also be studied.

Conditions

Leukemia

Keywords

Relapsed Acute Leukemia; Chronic Myelomonocytic Leukemia; CMML; Myelodysplastic Syndrome; MDS; Acute myeloid leukemia; AML; 5-azacitidine; Azacitidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816; Sorafenib; Nexavar; BAY43-9006

Outcome Measures

Primary Outcomes (1)

• Phase I: Maximum Tolerated Dose (MTD) of Sorafenib Given With Azacitidine

  MTD is defined as highest dose level in which 6 patients treated with at most 1 experiencing a dose limiting toxicity (DLT) during 1st cycle. One cycle of therapy is 7 days of azacitidine (AZA) and 28 days of sorafenib. Starting dose of Sorafenib is 200 mg twice a day azacitidine

  28 day cycle

Secondary Outcomes (1)

• Phase II: Number of Participants With Response

  90 days

Study Arms (1)

Azacitidine + Sorafenib

EXPERIMENTAL

Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days; Sorafenib 200 mg orally twice a day.

Drug: Azacitidine; Drug: Sorafenib

Interventions

Azacitidine DRUG

75 mg/m\^2 subcutaneously (SQ) or by vein (IV) daily for 7 days per 28 day cycle.

Also known as: 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Azacitidine + Sorafenib

Sorafenib DRUG

Starting dose level 200 mg by mouth two times a day in a 28 day cycle. In Phase II, Sorafenib administered per MTD dose from Phase I. Drug doses separated by approximately 12 hours.

Also known as: Nexavar, BAY43-9006

Azacitidine + Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with MDS, CMML or AML, who have failed pror therapy (including low and intermediate risk patient who have required prior therapy).
• Patients with MDS or CMML should have failed prior therapy with a hypomethylating agent and/or with lenalidomide. Patients who have received prior azacitidine are eligible if the treating physician feels that participation in the sudy is in the patients' best interest.
• Patients with AML should have failed any prior induction therapy or have relapsed after prior therapy.
• Patients with MDS or CMML who received therapy with hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for AML.
• Patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive or refuse standard therapy.
• Age of greater than or equal to 18 years of age.
• ECOG Performance Status less than or equal to 2.
• Adequate liver (bilirubin less than or equal 1.5 \* upper limit of normal (ULN), ALT and AST less than or equal 2.5 \* ULN and Alkaline phosphatase less than 4 \* ULN if not related to leukemic disease) and renal (creatinine less than or equal 1.5\* ULN) function. Amylase and Lipase must be less than or equal 2 \* ULN.
• Patients must provide written informed consent.
• Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the toxic effects of that therapy to at least grade 1. Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy but should be stopped for 24 hours prior to initiation of azacitidine.
• 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 azacytidine. 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 a 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. 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.
• INR less than 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 at least weekly, or as defined by the local standard of care, until INR is stable.

You may not qualify if:

• Nursing and pregnant females.
• Patients with acute promyelocytic leukemia are excluded unless multiply refractory and no other standard treatment strategies are available to them
• Patients with known allergy to sorafenib or azacitidine, mannitol or any of their components.
• Patients with known 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 poorly controlled 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).
• Patients who have had any major surgical procedure within 28 days of Day 1.
• Patients unwilling or unable to comply with the protocol.
• Patients with known malignant disease of the central nervous system or advanced malignant hepatic tumors.
• Cardiac disease: Congestive heart failure greater than class II 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.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure greater than 140 mmHg or diastolic pressure greater than 90 mmHg, despite optimal medical management.
• Active clinically serious infection greater than 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 greater than CTCAE v4. Grade 2 within 4 weeks of first dose of study drug.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator
• Onyx Therapeutics, Inc.: collaborator
• Celgene: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 30028037 DERIVED

• Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, Pierce S, Daver N, Garcia-Manero G, Faderl S, Nazha A, Konopleva M, Borthakur G, Burger J, Kadia T, Dellasala S, Andreeff M, Cortes J, Kantarjian H, Levis M. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62. doi: 10.1182/blood-2013-01-480228. Epub 2013 Apr 23.

  PMID: 23613521 DERIVED

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Farhad Ravandi-Kashani, Professor, Leukemia Department
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Farhad Ravandi-Kashani, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: December 7, 2010
• Study Start: January 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 6, 2016
• Results First Posted: May 6, 2016

Record last verified: 2016-03

Locations

US (1)