CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

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Brief Title

CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Official Title

A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent

Brief Summary

      This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin)
      works in treating patients with relapsed or refractory acute myeloid leukemia or
      myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways
      to stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing.
    

Detailed Description

      PRIMARY OBJECTIVES:

      Determine efficacy of CPX-351 by measuring the response rate as the sum of complete response
      (CR) and complete remission with incomplete count recovery (CRi) in older patients (age 60
      and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed
      after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher
      risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia
      (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML.

      SECONDARY OBJECTIVES:

        1. Determine the safety of CPX-351, as the frequency of Grade 3 to 5 SAEs

        2. Determine the duration of remission (DOR) following induction therapy with CPX-351.

        3. Determine overall survival (OS) at 12 months.

        4. Determine the early induction mortality (at 30 and 60 days) following CPX-351 following
           induction therapy.

      OUTLINE:

      Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) at a dose of 65
      units/m2/day over 90 minutes on days 1, 3, and 5 of each induction cycle.

        -  1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose
           of 65 units/m2/day over 90 minutes on days 1, 3, and 5. Patients achieving a complete
           remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 proceed to
           consolidation therapy

        -  2nd INDUCTION: Patients with reduced blast count not achieving a morphological leukemia
           free state (< 5% blasts) receive the 2nd course of induction therapy. Patients receive
           liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes
           on days 1 and 3. Patients achieving a complete remission (CR) or a CR with incomplete
           blood count recovery (CRi) after the 2nd course of induction therapy proceed to
           consolidation therapy.

        -  CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin
           CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.

      After completion of study treatment, patients are followed up for up to 1 year.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Response Rate (RR)

Secondary Outcome

 Complete Response With Incomplete Count Recovery (CRi)

Condition

Adult Acute Erythroid Leukemia (M6)

Intervention

liposomal cytarabine-daunorubicin CPX-351

Study Arms / Comparison Groups

 Liposomal cytarabine-daunorubicin CPX-351
Description:  1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5.
2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.
CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.

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

11

Start Date

February 3, 2014

Completion Date

December 18, 2017

Primary Completion Date

December 4, 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand and voluntarily give informed consent

          -  Age ≥ 60

          -  Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and
             high risk MDS by IPSS) along with one of the following:

               -  Patients with de novo or secondary MDS with progression/refractoriness after HMA
                  treatment who have not transformed to AML

               -  Patients with MDS and prior HMA treatment for MDS who transform to AML

               -  Patients with AML who are refractory/relapsed after HMA therapy for their AML are
                  eligible

          -  Life expectancy > 1 month

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Laboratory values fulfilling the following:

               -  Serum creatinine < 2.0 mg/dL

               -  Serum total bilirubin ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN

          -  Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography)
             or MUGA scan

          -  Patients with second malignancies may be eligible at discretion of PI given acute life
             threatening nature of untreated AML or higher risk MDS. Patients maintained on
             long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.

        Exclusion Criteria:

          -  Patients who have previously undergone allogeneic hematopoietic stem cell transplant
             will be excluded from this study

          -  Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368
             mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment
             of solid tumors). See appendix for anthracycline equivalence table.

          -  Acute promyelocytic leukemia [t(15;17)]

          -  Any serious medical condition, laboratory abnormality or psychiatric illness that
             would prevent obtaining informed consent

          -  Patients who have had conventional intensive cytotoxic induction chemotherapy for
             treatment of specifically MDS or AML are excluded.

          -  Patients who have not previously been treated with HMA therapy will be excluded

          -  Clinical evidence of active CNS leukemia

          -  Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable
             ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not
             controlled on medical therapy, uncontrolled hypertensive heart disease, and
             uncontrolled congestive heart failure)

          -  Active and uncontrolled infection. Patients with an active infection receiving
             treatment and hemodynamically stable for 48 hours may be entered into the study

          -  Known active uncontrolled HIV or hepatitis C infection

          -  Known hypersensitivity to cytarabine, daunorubicin or liposomal products

          -  Known history of Wilson's disease or other copper-related disorders

          -  Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
             which in the opinion of the investigator would compromise the patient's safety or
             interfere with data interpretation

          -  Laboratory abnormalities:

               -  Serum creatinine ≥ 2.0 mg/dL

               -  Serum total bilirubin > 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Rondeep Brar, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02019069

Organization ID

IRB-28524

Secondary IDs

NCI-2013-01982

Responsible Party

Sponsor-Investigator

Study Sponsor

Rondeep Brar

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Rondeep Brar, MD, Principal Investigator, Stanford University


Verification Date

January 2019