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

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ClinicalTrials.gov Identifier: NCT01893320
Recruitment Status : Active, not recruiting
First Posted : July 9, 2013
Last Update Posted : October 21, 2019
Sponsor:
Collaborator:
Sunesis Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: Vosaroxin Drug: Decitabine Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
Actual Study Start Date : July 18, 2013
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Vosaroxin + Decitabine

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

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.


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




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Vosaroxin in Combination with Decitabine [ Time Frame: 21 days ]
    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.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 21 days ]
    ORR defined as Complete response (CR) + Complete response without platelet recovery (CRp) + CR with insufficient hematological recovery (platelets or neutrophils (CRi).



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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. "
  3. Eastern Cooperative Oncology Group performance status </= 2.
  4. 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).
  5. Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
  6. Patients must be willing and able to review, understand, and provide written consent before starting therapy.
  7. 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.

Exclusion Criteria:

  1. 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.
  2. Myocardial infarction in the previous 12 weeks (from the start of treatment).
  3. Active and uncontrolled disease/infection as judged by the treating physician
  4. Pregnant or breastfeeding
  5. Known Human Immunodeficiency Virus seropositivity
  6. 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
  7. Acute promyelocytic leukemia (APL).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01893320


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Sunesis Pharmaceuticals
Investigators
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Principal Investigator: Naval Daver, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01893320     History of Changes
Other Study ID Numbers: 2013-0099
NCI-2013-01665 ( Registry Identifier: NCI CTRP )
First Posted: July 9, 2013    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myeloid Leukemia
AML
High-risk Myelodysplastic Syndrome
MDS
Chronic Myelomonocytic Leukemia
CMM
Maximum tolerated dose
MTD
Vosaroxin
Decitabine
Dacogen
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors