Clinical Trials /

Investigator Initiated Trial of CPX-351 for Untreated Acute Myeloid Leukemia

NCT03335267

Description:

This is an open label study to assess the suitability of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML. Patients may have received prior AML treatment with non-intensive regimens, e.g. hypomethylating agents, low dose Ara C or lenolidomide, but may not have received intensive AML treatment with anthracyclines and/or cytarabine prior to enrollment on this trial. The outcome of elderly patients following intensive treatment with CPX-351 will be measured by clinical endpoints for efficacy and safety and by biological/functional response.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Investigator Initiated Trial of CPX-351 for Untreated Acute Myeloid Leukemia
  • Official Title: Phase II Trial of CPX (Cytarabine:Daunorubicin) Liposome Injection in Patients >/=60 Years of Age With AML Previously Untreated By Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 1510016710
  • NCT ID: NCT03335267

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
CPX-351CPX-351 (Cytarabine:Daunorubicin) Injection

Purpose

This is an open label study to assess the suitability of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML. Patients may have received prior AML treatment with non-intensive regimens, e.g. hypomethylating agents, low dose Ara C or lenolidomide, but may not have received intensive AML treatment with anthracyclines and/or cytarabine prior to enrollment on this trial. The outcome of elderly patients following intensive treatment with CPX-351 will be measured by clinical endpoints for efficacy and safety and by biological/functional response.

Trial Arms

NameTypeDescriptionInterventions
CPX-351 (Cytarabine:Daunorubicin) InjectionExperimentalDosing for first induction: CPX-351 • CPX-351 at 100u/m2 will be administered on study days 1, 3 and 5 Dosing for second induction: • CPX-351 at 100 u/m2 will be administered on days 1 and 3 Dosing for consolidation: • CPX-351 at 65 u/m2 will be administered on days 1 and 3
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand and voluntarily give informed consent

          -  Age≥60 years at the time of study treatment

          -  Pathological diagnosis of AML according to WHO criteria (with >20% blasts in the
             peripheral blood or bone marrow) including:

          -  De novo AML with normal karyotype or adverse karyotypes (including patients with
             karyotypic abnormalities characteristic of MDS)

          -  Secondary AML: transformed from prior MDS or MPN, confirmed by bone marrow
             documentation of prior antecedent hematologic disorder

          -  Therapy-related AML: t-AML, requires documented history of prior cytotoxic therapy or
             ionizing radiotherapy for an unrelated disease

          -  Performance status >50% KPS, ECOG 0-2

          -  Laboratory values fulfilling the following:

          -  Serum creatinine < 2.5 mg/dL

          -  Serum total bilirubin < 2.5 mg/dL,

          -  Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN

          -  Patients with elevated liver enzymes and serum creatinine values secondary to AML are
             eligible after discussion with PI

          -  Cardiac ejection fraction ≥ 50% by echocardiography or MUGA

          -  Patients with history of second malignancies in remission may be eligible if there is
             clinical evidence of disease stability off cytotoxic chemotherapy, documented by
             imaging, tumor marker studies, etc., at screening. Patients maintained on long-term
             non-chemotherapy treatment, e.g., hormonal therapy, are eligible.

        Exclusion Criteria:

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

          -  Clinical evidence of active CNS leukemia

          -  Prior intensive chemotherapy for AML with anthracycline/cytarabine-based regimens and/
             or prior HSCT. Patients may have been treated with commercially available or
             investigational hypomethylating agents (e.g. decitabine, azacitidine, SGI-110),
             lenalidomide, or low-dose cytarabine (not to exceed 20 mg/m2 daily for 14 days for ≤ 6
             cycles)

          -  Prior treatment including HMA, systemic chemotherapy, surgery, or radiation therapy
             must have been completed at least 7 days before start of study treatment or after
             discussion with PI. Treatment with investigational agents must have been completed at
             least 14 days prior to study drug treatment. Hydroxyurea is permitted for control of
             blood counts before the start of study treatment. Toxicities associated with prior
             therapies must have recovered to grade 1 or less prior to start of study treatment.

          -  Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2
             daunorubicin (or equivalent).

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

          -  Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart
             disease, significant valvular dysfunction, hypertensive heart disease, and congestive
             heart failure) resulting in heart failure by New York Heart Association Criteria
             (Class III or IV staging)

          -  Active or uncontrolled infection. Patients with an infection receiving treatment
             (antibiotic, antifungal or antiviral treatment) may be entered into the study but must
             be afebrile and hemodynamically stable for ≥72 hrs.

          -  Patients with current or recent evidence of invasive fungal infection (blood or tissue
             culture); patients with recent fungal infection must have a subsequent negative
             cultures to be eligible

          -  Known HIV (new testing not required) or evidence of active hepatitis B or C infection
             (with rising transaminase values)

          -  Hypersensitivity to cytarabine, daunorubicin or liposomal products

          -  History of Wilson's disease or other copper-metabolism disorder

          -  History of prior bone marrow or solid organ transplantation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of the feasibility of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML based on safety and efficacy.
Time Frame:5 years
Safety Issue:
Description:CPX-351 alone will be declared feasible if one or two induction courses (3 doses or 5 doses) can be delivered to patients with acceptable 30-day mortality.

Secondary Outcome Measures

Measure:Efficacy of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML by bone marrow biopsy determination of treatment response rate.
Time Frame:Up to 5 years, as needed.
Safety Issue:
Description:The efficacy of CPX-351 in this population will be assessed by treatment response rate, as determined by bone marrow analysis at Day 14 of each induction and consolidation, and as needed thereafter, up to 5 years.
Measure:Safety of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML by evaluation of the frequency and severity of adverse events.
Time Frame:5 years
Safety Issue:
Description:The safety of CPX-351 in this population will be assessed by evaluation of the frequency and severity of adverse events.
Measure:Quality of Life Assessment using the Functional Assessment of Cancer Therapy-Leukemia (FACT-LEU).
Time Frame:5 years
Safety Issue:
Description:The higher the score, the better the QOL. Physical Well-Being (PWB): Range:0-28. To derive: Subtract the answer from "4" for each of 7 questions. Add scores, multiply by 7 and divide by # of questions answered. Social/Family Well-Being (SWB): Range:0-28. To derive: Add answers of 7 questions, multiply by 7 and divide by # of questions answered. Emotional Well-Being (EWB): Range:0-24. To derive: Subtract the answers from "4" for each of the 6 questions, except #2 (added without modification). Add values, multiply by 6 and divide by # of questions answered. Functional Well-Being (FWB): Range:0-28. To derive: Add answers of 7 questions, multiply by 7 and divide by # of questions answered. Leukemia Subscale (LeuS): Range:0-68. To derive: Subtract the answers from "4" for each of the 17 questions, except #s 11 and 12 (these are added without modification). Add values, multiply by 17 and divide by # of questions answered. FACT-Leu total =PWB+SWB+EWB+FWB+LeuS. Range: 0-176.
Measure:Cognitive function
Time Frame:5 years
Safety Issue:
Description:The relationship of cognitive function to outcome will be assessed using the Blessed Orientation-Memory-Concentration Test
Measure:Cognitive function
Time Frame:5 years
Safety Issue:
Description:The relationship of cognitive function to outcome will be assessed using the Montreal Cognitive Assessment.
Measure:Rate of morphologic leukemia-free state (MLFS)
Time Frame:5 years
Safety Issue:
Description:The rate of morphologic leukemia-free state (MLFS) will be determined to supplement the efficacy assessment of CPX-351.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

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