Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome

NCT01893320 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2013-0099NCI-2013-01665
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of vosaroxin and decitabine can help to control AML or MDS. The safety of these drugs will also be studied.

Conditions

Leukemia

Keywords

Leukemia; Acute Myeloid Leukemia; AML; High-risk Myelodysplastic Syndrome; MDS; Chronic Myelomonocytic Leukemia; CMM; Maximum tolerated dose; MTD; Vosaroxin; Decitabine; Dacogen

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Vosaroxin in Combination With Decitabine

  Maximum tolerated dose (MTD) defined as highest daily oral dose evaluated at which \<33% of patients experience a dose limiting toxicity (DLT). A non-hematologic dose-limiting toxicity (DLT) defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to CTCAE criteria) assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 28 days on study. A hematologic DLT defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy. This will define severe and delayed myelosuppression not related to persistent leukemia and likely related to treatment.

  21 days

Secondary Outcomes (1)

• Participants With a Response

  21 days

Study Arms (1)

Vosaroxin + Decitabine

EXPERIMENTAL

The first 6 patients on study (first cohort) receive 1 or 2 induction cycles of therapy according to the following starting schedule: Vosaroxin administered intravenously on days 1 and 4 at a dose of 90 mg/m2 in the first cycle (induction 1) for a total dose of 180 mg/m2/cycle in combination with Decitabine at a dose of 20 mg/m2 intravenously daily for 5 consecutive days (Days 1 to 5). Following the phase I portion, patients in phase II receive the following induction: 1. Vosaroxin intravenously on days 1 and 4 at a dose of 70 mg/m2 for a total dose of 140 mg/m2/cycle (days 1 and 4), or the final induction dose (MTD) determined in phase I. 2. Decitabine intravenously at a dose of 20 mg/m2 for 5 consecutive days (days 1 to 5), or the final induction dose (MTD) determined in phase I.

Drug: Vosaroxin; Drug: Decitabine

Interventions

Vosaroxin DRUG

Phase I Starting Dose: 90 mg/m2 by vein on Days 1 and 4 of each cycle. Phase II Starting Dose: 70 mg/m2 by vein on Days 1 and 4 of each cycle, or maximum tolerated dose from Phase I.

Vosaroxin + Decitabine

Decitabine DRUG

Phase I and II: 20 mg/m2 by vein daily for 5 consecutive days (Days 1 to 5).

Also known as: Dacogen

Vosaroxin + Decitabine

Eligibility Criteria

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

You may qualify if:

• Previously untreated AML (\>/= 20% blasts). Patients with high-risk MDS (defined as having \>/= 10% blasts in the bone marrow) or patients with Chronic Myelomonocytic Leukemia (CMML) (having \>/= 10% blasts in the bone marrow) may also be eligible after discussion with Principal Investigator (PI). Prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed. Patients may have received one dose of cytarabine (up to 2 g/m2) administered at presentation for control of hyperleucocytosis. For patients with prior MDS or CMML who transformed to AML, therapy received for MDS is not considered as prior therapy for AML.
• Age \>/= 60 years and not candidates for conventional cytotoxic chemotherapy or refuse it; OR patients below the age of 60 years who are considered unfit and/or unable to tolerate standard chemotherapy at the discretion of the treating physician or the principal investigator. "
• Eastern Cooperative Oncology Group performance status \</= 2.
• Adequate hepatic (serum total bilirubin \</= 1.5 x upper limit normal (ULN), alanine aminotransferase and/or aspartate transaminase \</= 2.5 x ULN) and renal function (creatinine \</= 2.0 mg/dL).
• Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Patients must be willing and able to review, understand, and provide written consent before starting therapy.
• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum pregnancy test within 14 days before the start of the treatment. Women of childbearing potential may have a urine pregnancy test, instead of a serum pregnancy test. If either the serum or urine pregnancy test is equivocally negative the patient will be eligible for the protocol. Women of childbearing potential must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment.

You may not qualify if:

• New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as active angina pectoris, clinically significant cardiac arrhythmia that requires therapy in the opinion of the treating physician or PI, uncontrolled hypertension (blood pressure \> 160 systolic and \> 110 diastolic not responsive to antihypertensive medication), uncontrolled diabetes mellitus in the opinion of the treating physician or PI, or uncontrolled congestive heart failure in the opinion of the treating physician or PI.
• Myocardial infarction in the previous 12 weeks (from the start of treatment).
• Active and uncontrolled disease/infection as judged by the treating physician
• Pregnant or breastfeeding
• Known Human Immunodeficiency Virus seropositivity
• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
• Acute promyelocytic leukemia (APL).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Sunesis Pharmaceuticals: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Daver N, Kantarjian H, Garcia-Manero G, Jabbour E, Borthakur G, Brandt M, Pierce S, Vaughan K, Ning J, Nogueras Gonzalez GM, Patel K, Jorgensen J, Pemmaraju N, Kadia T, Konopleva M, Andreeff M, DiNardo C, Cortes J, Ward R, Craig A, Ravandi F. Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Haematologica. 2017 Oct;102(10):1709-1717. doi: 10.3324/haematol.2017.168732. Epub 2017 Jul 20.

  PMID: 28729302 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Interventions

vosaroxin; Decitabine

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)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Naval Daver MD, Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

NDaver@mdanderson.org

713-794-4392

Study Officials

• Naval Daver, MD

  M.D. 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: July 2, 2013
• First Posted: July 9, 2013
• Study Start: July 18, 2013
• Primary Completion: January 11, 2021
• Study Completion: January 11, 2021
• Last Updated: February 9, 2022
• Results First Posted: February 9, 2022

Record last verified: 2022-01

Locations

US (1)