E7070, Idarubicin and Cytarabine in Relapsed AML and High-Risk Myelodysplastic Syndromes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01692197
First received: September 20, 2012
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

The goal of this clinical research study is to learn if E7070 in combination with idarubicin, cytarabine, and dexamethasone can help to control the disease in patients with either AML or high-risk MDS that has relapsed. The safety of the drug combination will also be studied.


Condition Intervention Phase
Leukemia
Drug: E7070
Drug: Idarubicin
Drug: Cytarabine
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of E7070, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Response [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    Efficacy measured by overall response - complete response plus complete response with incomplete platelet recovery, plus partial response (CR + CRp + PR+ marrow clearance of blast) during Stage 1 and 2. The sample size and stopping rules determined according to Simon's two-stage design. Overall response (CR + CRp + PR) rate and its 95% confidence interval estimated using a binomial distribution. Overall survival and progression free survival functions estimated using the Kaplan-Meier method.

  • Toxicity Profile [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Bayesian sequential monitoring method (Thall, 1995) used to monitor toxicity. Toxic event defined as death or a CTCAE 4.0 grade 3/4 non-hematological toxicity related to study drug lasting or 7 days or more. Toxicity reported by type, frequency and severity. Worst toxicity grades per patient tabulated for selected adverse events and laboratory measurements.


Estimated Enrollment: 40
Study Start Date: February 2013
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stage 1: E7070
Stage 1: E7070 400 mg/m2 by vein (IV) over 1 hour on day 1 and day 8 (+/- 2 days on Day 8 only). If at assessment patient is found to be in CR, CRp, PR or marrow clearance of blasts, the patient may receive post-remission therapy with E7070 400 mg/m2 IV over 1 hour on day 1 and day 8 (+/- 2 days on Day 8 only) every 3 weeks for up to five additional cycles as long as patient continues to have clinical benefit.
Drug: E7070
400 mg/m2 intravenously over 1 hour on Day 1 and Day 8 every 3 weeks.
Experimental: Stage 2: E7070 + Idarubicin + Cytarabine
Stage 2: E7070 400 mg/m2 IV over 1 hour on day 1 and day 8 (+/- 2 days on Day 8 only) followed by, Idarubicin 8 mg/m2 IV over 1 hour daily for 3 days (days 9-11) and Cytarabine 1.0 g/m2 IV over 24 hours daily on day 9-12 (age <60 years) or days 9-11 (age > 60 years). Dexamethasone 10 mg IV daily for 3-4 days with cytarabine.
Drug: E7070
400 mg/m2 intravenously over 1 hour on Day 1 and Day 8 every 3 weeks.
Drug: Idarubicin
8 mg/m2 by vein over 1 hour daily for 3 days (Days 9-11).
Other Name: Idamycin
Drug: Cytarabine
1.0 g/m2 by vein daily on Days 9 - 12 (age <60 years) or Days 9 - 11 (age > 60 years).
Other Names:
  • ARA-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Dexamethasone
10 mg by vein daily for 3 - 4 days with cytarabine.
Other Name: Decadron

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients with histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) [except acute promyelocytic leukemia], or high-risk myelodysplastic syndrome (HRMDS) (Int-2 high risk by IPSS or >10% blasts in marrow).
  2. Patients must be 18 years or older.
  3. Patients must have a performance status of 0-2 (Zubrod scale).
  4. Patients must have adequate renal function (serum creatinine less than or equal to 1.3 mg/dL and/or creatinine clearance > 40 mL/min). Patients with renal dysfunction due to organ infiltration by disease may be eligible after discussion with the Principal Investigator (PI) (up to creatinine less than or equal to 2.0), and appropriate dose adjustments will be considered.
  5. Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; SGOT or SGPT less than or equal to 3X the ULN for the reference lab unless due to leukemia or congenital hemolytic disorder or bilirubin). Patients with hepatic dysfunction (SGOT/SGPT up to less than or equal to 5 X ULN) due to organ infiltration by disease may be eligible after discussion with the PI, and appropriate dose adjustments will be considered.
  6. Patients must have normal cardiac ejection fraction
  7. QTc interval </= 480 msecs.
  8. Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
  9. Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.

Exclusion Criteria:

  1. Patients must not have untreated or uncontrolled life-threatening infection.
  2. Patients must not have received chemotherapy and/or radiation therapy within 2 weeks. Hydroxyurea is allowed up to 48 hours prior to starting therapy in the setting of rapidly proliferating disease. Use of hydroxyurea to control proliferative disease will be allowed starting from day 2 until day 7 Cycle 1. Maximum dose of hydroxyurea allowed daily is 5 gram and hydroxyurea must be discontinued once administration of idarubicin and cytarabine is started.
  3. Any other medical condition, including mental illness or substance abuse, deemed by the PI to be likely to interfere with a patient's ability to sign informed consent or cooperate and participate in the study or with the interpretation of the results.
  4. Patients must not have received an investigational anti-cancer drug within two weeks of E7070 administration.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01692197

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Eisai Inc.
Investigators
Principal Investigator: Gautam Borthakur, MBBS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01692197     History of Changes
Other Study ID Numbers: 2009-0570, NCI-2012-02065
Study First Received: September 20, 2012
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myeloid Leukemia
Acute Myelogenous Leukemia
AML
Relapsed or Refractory
High-Risk Myelodysplastic Syndromes
HRMDS
E7070
Idarubicin
Idamycin
Cytarabine
ARA-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride
Dexamethasone
Decadron

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Leukemia, Myeloid
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
BB 1101
Cytarabine
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Idarubicin
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antiviral Agents
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 22, 2014