Sorafenib and Low Dose Cytarabine in Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT00516828 | Completed Phase 1 DMC

• 3 other identifiers: I186CAN-NCIC-IND186CDR0000560975
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cytarabine may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving sorafenib together with cytarabine and to see how well it works in treating older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); untreated adult acute myeloid leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (3)

• Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I)

  29 months

• Dose-limiting toxicity (Phase I)

  29 months

• Complete remission (Phase II)

  29 months

Secondary Outcomes (5)

• Overall response rate (complete and partial response) (Phase II)

  29 months

• Time to progression (Phase II)

  29 months

• Overall survival (Phase II)

  29 months

• FLT-3 ITD endpoint mutation response correlation.

  29 months

• Toxicity (Phase II)

  29 months

Study Arms (1)

Sorafenib and Cytarabine

EXPERIMENTAL

Cytarabine: subcutaneously twice daily from day 1 - 10. Sorafenib: Days 2-28; at the dose level assigned at registration. Sorafenib will be given orally twice daily.

Drug: cytarabine

Interventions

cytarabine DRUG

subcutaneously twice daily from Day 1 to 10

Sorafenib and Cytarabine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute myeloid leukemia (AML) by FAB criteria (By morphology and routine histochemistry and confirmed, when possible, by flow cytometric analysis of surface immunophenotype; co-expression of lymphoid markers permitted) * High-risk myelodysplastic syndromes defined as IPSS category of intermediate-2 or greater * Must be considered unsuitable for intensive chemotherapy regimens * No documented CNS involvement PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * AST and ALT ≤ 2 times upper limit of normal (ULN) * Bilirubin normal * Creatinine ≤ 1.2 times ULN OR creatinine clearance ≥ 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ carcinoma of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years * No upper gastrointestinal or other conditions that would preclude compliance with or administration of oral medication * No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including any of the following: * History of significant neurologic or psychiatric disorder that would impair the ability to obtain consent * Active, uncontrolled, serious infections * Active peptic ulcer disease * Evidence of bleeding diathesis * No myocardial infarction within the past 6 months * No congestive heart failure * No unstable angina * No active cardiomyopathy or unstable ventricular arrhythmia * No poorly controlled hypertension (e.g., systolic BP ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg) * No known hypersensitivity to the study drugs or their components * No preexisting hypothyroidism prior to enrollment unless patient is euthyroid on medication * No neuropathy ≥ grade 2 PRIOR CONCURRENT THERAPY: * At least 2 days since prior hydroxyurea * No other prior chemotherapy * No concurrent therapeutic doses (≥ 2 mg/day) of anticoagulants (e.g., warfarin) * Doses of up to 2 mg/day given for prophylaxis of thrombosis are accepted provided INR is ≤ 1.5 * No other concurrent experimental drugs or anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Bayer: collaborator

Study Sites (4)

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• Macdonal DA, Assouline SE, Brandwein J, Kamel-Reid S, Eisenhauer EA, Couban S, Foo A, Leber B. Phase I/II study of low-dose cytarabine with sorafenib as first-line therapy of elderly patients with AML or high-risk myelodysplastic syndrome. J Clin Oncology 28[15s, abstr 6564]. 2010.

  RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Brian Leber, MD, FRCPC

  McMaster Children's Hospital at Hamilton Health Sciences

  STUDY CHAIR

• David A. MacDonald, MD

  Nova Scotia Cancer Centre

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: August 14, 2007
• First Posted: August 15, 2007
• Study Start: November 27, 2007
• Primary Completion: March 18, 2010
• Study Completion: January 10, 2013
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)