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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University
ClinicalTrials.gov Identifier:
NCT02019069
First received: November 25, 2013
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

This phase II clinical trial studies how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-35, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Adult Acute Erythroid Leukemia (M6)
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Drug: liposomal cytarabine-daunorubicin CPX-351
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Incidence of mortality assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: At day 30 ] [ Designated as safety issue: Yes ]
    To analyze the safety data, adverse events recorded using CTCAE 4.0 for each patient will reviewed and totaled, for the total number of adverse events for each adverse event compared to total group of patients (rate of outcome of each adverse event in study population).

  • Incidence of mortality assessed using the CTCAE version 4.0 [ Time Frame: At day 60 ] [ Designated as safety issue: Yes ]
    To analyze the safety data, adverse events recorded using CTCAE 4.0 for each patient will reviewed and totaled, for the total number of adverse events for each adverse event compared to total group of patients (rate of outcome of each adverse event in study population).

  • Incidence of serious adverse events as assessed by CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of treatment ] [ Designated as safety issue: Yes ]
    To analyze the safety data, adverse events recorded using CTCAE 4.0 for each patient will reviewed and totaled, for the total number of adverse events for each adverse event compared to total group of patients (rate of outcome of each adverse event in study population).

  • Frequency of grade 3-5 adverse events as assessed by CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of treatment ] [ Designated as safety issue: Yes ]
    To analyze the safety data, adverse events recorded using CTCAE 4.0 for each patient will reviewed and totaled, for the total number of adverse events for each adverse event compared to total group of patients (rate of outcome of each adverse event in study population).

  • Response rate (CR + CRi) following induction therapy using the European Leukemia Net classification for AML and the International Working Group guidelines for MDS [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    The response rate will be calculated by adding the total CR + CRi (total number of CR + CRi for AML + CR for MDS) events after up to two courses of induction therapy, and comparing it to the total number of patients undergoing induction with CPX-351.


Secondary Outcome Measures:
  • Duration of remission following induction with CPX-351 [ Time Frame: From the start of response until disease relapse or death, assessed up to 1 year ] [ Designated as safety issue: No ]
    Calculated by counting the number of days from the date of remission until date of disease relapse for patients who achieve a CR (and CRi for AML). The average days of remission will be calculated to determine the median duration of remission.

  • Overall survival [ Time Frame: From the date of entry into trial to death from any cause, assessed at 12 months ] [ Designated as safety issue: No ]
    Determined by the number of patients who are alive at 12 months compared to the number of patients who initiated into the study.

  • Early induction mortality after first induction [ Time Frame: Day 60 ] [ Designated as safety issue: Yes ]
    Calculated by determining the number of deaths within the first 60 days, using day 1 of the first induction therapy as the first day, compared to the total number of patients who have received any dose of CPX-351.


Estimated Enrollment: 33
Study Start Date: February 2014
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (liposomal cytarabine-daunorubicin CPX-351)

INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV 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. Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive a second course of induction therapy liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Patients achieving a CR or a CRi at day 14 or after a second course of induction therapy proceed to consolidation therapy.

SECOND INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3.

CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment may repeat after 28-75 days in the absence of disease progression or unacceptable toxicity.

Drug: liposomal cytarabine-daunorubicin CPX-351
Given IV
Other Name: CPX-351
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the efficacy and safety profile of the use of CPX-351 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:

I. Determine the duration of remission following induction therapy with CPX-351.

II. Determine overall survival at 12 months. III. Determine the early induction mortality (at 60 days) following CPX-351 in this cohort following induction therapy.

OUTLINE:

INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive a second course of induction therapy. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 or after a second course of induction therapy proceed to consolidation therapy.

SECOND INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3.

CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Patients may receive a second course after 28-75 days in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and voluntarily give informed consent
  • Pathological diagnosis of AML (by World Health Organization [WHO] criteria) or higher risk MDS (includes int-2 and high risk MDS by International Prognostic Scoring System (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 are eligible only if they are age > 75; those age 60-75 are not eligible for this study
    • 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
  • 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 upper limit of normal (ULN)
  • Cardiac ejection fraction >= 45% by echocardiography (transthoracic echocardiography) or multi gated acquisition scan (MUGA) scan
  • Patients with second malignancies may be eligible at discretion of principal investigator (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
  • All patients must meet one of the qualifications as outlined below after prior HMA therapy:

    • Relapse after CR/CRi or partial remission (PR)—1 or more of the following:

      • Return to pretreatment bone marrow blast percentage (for initial PR)
      • Reappearance of bone marrow blasts (> 5%) following initial CR/CRi
    • Disease progression

      • For patients with 10% to 20% blasts: a 50% or more increase to more than 20% blasts
      • For patients with > 20% blasts: a 50% or more increase to more than 40% blasts
    • Refractory disease

      • No evidence of a response (CR, CRi, PR) following, at least, 6 cycles of hypomethylating agent

Exclusion Criteria:

  • Patients who have previously had > 368 mg/m^2 cumulative dose of daunorubicin or > 368 mg/m^2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors)
  • 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 less than 75 years of age with a history of documented MDS and HMA treatment for MDS that has transformed to AML are not eligible
  • Patients who have not previously been treated with HMA therapy will be excluded
  • Clinical evidence of active central nervous system (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 human immunodeficiency virus (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
  • 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
  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: NCT02019069

Locations
United States, California
Stanford University Cancer Institute Recruiting
Stanford, California, United States, 94305
Contact: Jack Taw    650-723-1269    jtaw@stanford.edu   
Principal Investigator: Bruno C. de Medeiros         
Sponsors and Collaborators
Bruno C. Medeiros
Investigators
Principal Investigator: Bruno de Medeiros Stanford University Hospitals and Clinics
  More Information

No publications provided

Responsible Party: Bruno C. Medeiros, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT02019069     History of Changes
Other Study ID Numbers: HEM0036, NCI-2013-01982, 4593, HEM0036, P30CA124435, 28524
Study First Received: November 25, 2013
Last Updated: March 16, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Congenital Abnormalities
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 27, 2014