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

This study is currently recruiting participants.
Verified June 2017 by Bruno C. Medeiros, Stanford University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02019069
First Posted: December 24, 2013
Last Update Posted: June 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University
November 25, 2013
December 24, 2013
June 14, 2017
February 2014
July 2019   (Final data collection date for primary outcome measure)
  • Incidence of mortality assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: At day 30 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Same as current
Complete list of historical versions of study NCT02019069 on ClinicalTrials.gov Archive Site
  • 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 ]
    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 ]
    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 ]
    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.
Same as current
Not Provided
Not Provided
 
CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
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
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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
    Given IV
    Other Name: CPX-351
  • Other: laboratory biomarker analysis
    Correlative studies
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.

Interventions:
  • Drug: liposomal cytarabine-daunorubicin CPX-351
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
33
December 2019
July 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
60 Years and older   (Adult, Senior)
No
Contact: Jack Taw 650-723-2781 jtaw@stanford.edu
United States
 
 
NCT02019069
HEM0036
NCI-2013-01982 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
4593
HEM0036 ( Other Identifier: Stanford University Hospitals and Clinics )
P30CA124435 ( U.S. NIH Grant/Contract )
28524 ( Other Identifier: Stanford IRB Number )
Not Provided
Not Provided
Not Provided
Bruno C. Medeiros, Stanford University
Bruno C. Medeiros
National Cancer Institute (NCI)
Principal Investigator: Rondeep Brar, MD Stanford University
Stanford University
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP