CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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Brief Title

CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Brief Summary

      This phase I trial studies the side effects and best dose of CPI-613 when given together with
      cytarabine and mitoxantrone hydrochloride in treating patients with relapsed or refractory
      acute myeloid leukemia. Drugs used in chemotherapy, such as CPI-613, cytarabine and
      mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either
      by killing the cells or by stopping them from dividing. CPI-613 may help cytarabine and
      mitoxantrone hydrochloride work better by making cancer cells more sensitive to the drugs
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and maximum tolerated dose (MTD) of CPI-613 when administered with
      high dose cytarabine, and mitoxantrone (mitoxantrone hydrochloride).

      SECONDARY OBJECTIVES:

      I. To determine the pharmacokinetics (PKs) of CPI-613 following intravenous (IV)
      administration in combination with high dose cytarabine and mitoxantrone.

      II. To observe the response rate (complete response [CR], complete response with incomplete
      platelet recovery [CRi] and partial response [PR]) of CPI-613 in combination with high dose
      cytarabine and mitoxantrone.

      III. To observe the overall survival of patients treated with CPI-613 in combination with
      high dose cytarabine and mitoxantrone.

      OUTLINE: This is a dose-escalation study of CPI-613.

      Patients receive CPI-613 intravenously (IV) over 2 hours on days 1-5, cytarabine IV over 3
      hours every 12 hours for 5 doses beginning on day 3, and mitoxantrone hydrochloride IV over
      15 minutes after the 1st, 3rd, and 5th doses of cytarabine. . Treatment repeats every 14 days
      for up to 2 courses* in the absence of disease progression or unacceptable toxicity.

      NOTE: *Patients undergoing a second course of therapy receive CPI-613 IV over 2 hours on days
      1-3, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 2, and
      mitoxantrone hydrochloride IV over 15 minutes after the 1st and 3rd doses of cytarabine.

      After completion of study treatment, patients are followed up for 6 months.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

MTD of CPI-613 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 3.0)

Secondary Outcome

 Response rate (CR, CRi, and PR)

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

CPI-613

Study Arms / Comparison Groups

 Treatment (CPI-613, cytarabine, mitoxantrone hydrochloride)
Description:  Patients receive CPI-613 IV over 2 hours on days 1-5, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 3, and mitoxantrone hydrochloride IV over 15 minutes after the 1st, 3rd, and 5th doses of cytarabine. Treatment repeats every 14 days for up to 2 courses* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients undergoing a second course of therapy receive CPI-613 IV over 2 hours on days 1-3, cytarabine IV over 3 hours every 12 hours for 5 doses beginning on day 2, and mitoxantrone hydrochloride IV over 15 minutes after the 1st and 3rd doses of cytarabine.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

67

Start Date

January 2013

Completion Date

January 2016

Primary Completion Date

January 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically documented relapsed and/or
             refractory acute myeloid leukemia

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3

          -  Expected survival > 3 months

          -  Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
             sterile) must use accepted contraceptive methods (abstinence, intrauterine device
             [IUD], oral contraceptive or double barrier device), and must have a negative serum or
             urine pregnancy test within 1 week prior to treatment initiation; (Note: Pregnant
             patients are excluded because the effects of CPI-613 on a fetus are unknown)

          -  Fertile men must practice effective contraceptive methods during the study period,
             unless documentation of infertility exists

          -  Mentally competent, ability to understand and willingness to sign the informed consent
             form

          -  No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with
             biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with
             CPI-613; patients must have fully recovered from the acute, non-hematological,
             non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or
             other anti-cancer modalities (returned to baseline status as noted before most recent
             treatment); patients with persisting, non-hematologic, non-infectious toxicities from
             prior treatment ≤ grade 2 are eligible, but must be documented as such

          -  Aspartate aminotransferase ([AST]/serum glutamic oxaloacetic transaminase [SGOT]) =< 3
             x upper normal limit (UNL), alanine aminotransferase ([ALT]/serum glutamate pyruvate
             transaminase [SGPT]) =< 3 x UNL (=< 5 x upper limit of normal [ULN] if liver
             metastases present)

          -  Bilirubin =< 1.5 x UNL

          -  Serum creatinine =< 1.5 mg/dL or 133 μmol/L

          -  International Normalized Ratio or INR must be < 1.5

        Exclusion Criteria:

          -  Serious medical illness, such as significant cardiac disease (e.g. symptomatic
             congestive heart failure, unstable angina pectoris, myocardial infarction within the
             past 6 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart
             Association class III or IV), or severe debilitating pulmonary disease, that would
             potentially increase patients' risk for toxicity

          -  Patients with active central nervous system (CNS) or epidural tumor

          -  Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g.,
             active peptic ulcer disease)

          -  Pregnant women, or women of child-bearing potential not using reliable means of
             contraception (because the teratogenic potential of CPI-613 is unknown)

          -  Lactating females because the potential of excretion of CPI-613 into breast milk
             (Note: Lactating females are excluded because the effects of CPI-613 on a nursing
             child are unknown)

          -  Fertile men unwilling to practice contraceptive methods during the study period

          -  Life expectancy less than 3 months

          -  Any condition or abnormality which may, in the opinion of the investigator, compromise
             the safety of patients

          -  Unwilling or unable to follow protocol requirements

          -  Patients with large and recurrent pleural or peritoneal effusions requiring frequent
             drainage (e.g. weekly); patients with any amount of clinically significant pericardial
             effusion

          -  Active heart disease including myocardial infarction within previous 6 months,
             symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic
             congestive heart failure

          -  Albumin < 2.0 g/dL or < 20 g/L

          -  Evidence of ongoing, uncontrolled infection

          -  Patients with known human immunodeficiency virus (HIV) infection; (Note: Patients with
             known HIV infection are excluded because patients with an immune deficiency are at
             increased risk of lethal infections when treated with marrow-suppressive therapy, and
             because there may be unknown or dangerous drug interactions between CPI-613 and
             anti-retroviral agents used to treat HIV infections)

          -  Patients receiving any other standard or investigational treatment for their cancer,
             or any other investigational agent for any indication within the past 2 weeks prior to
             initiation of CPI-613 treatment (the use of Hydrea is allowed)

          -  Patients who have received immunotherapy of any type within the past 4 weeks prior to
             initiation of CPI-613 treatment

          -  Requirement for immediate palliative treatment of any kind including surgery

          -  Patients that have received a chemotherapy regimen with stem cell support in the
             previous 6 months

          -  A history of additional risk factors for torsade de pointes (e.g., clinically
             significant heart failure, hypokalemia, family history of long QT syndrome)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Timothy Pardee, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01768897

Organization ID

IRB00022138

Secondary IDs

NCI-2012-02768

Responsible Party

Sponsor

Study Sponsor

Wake Forest University Health Sciences

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Timothy Pardee, Principal Investigator, Wake Forest University Health Sciences


Verification Date

June 2018