Clinical Trials /

Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome

NCT03672539

Description:

This phase II trial studies the side effects and how well liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin work in treating patients with acute myeloid leukemia that has come back or that does not respond to treatment or high risk myelodysplastic syndrome. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome
  • Official Title: A Pilot Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Patients With Acute Myeloid Leukemia (AML) and Post-Hypomethylating Agent (Post-HMA) Failure High-Risk Myelodysplastic Syndrome (HR-MDS).

Clinical Trial IDs

  • ORG STUDY ID: 2018-0235
  • SECONDARY ID: NCI-2018-01812
  • SECONDARY ID: 2018-0235
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03672539

Conditions

  • CD33 Positive
  • High Risk Myelodysplastic Syndrome
  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Gemtuzumab OzogamicinCalicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676Treatment (CPX-351, gemtuzumab ozogamicin)
Liposome-encapsulated Daunorubicin-CytarabineCPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, VyxeosTreatment (CPX-351, gemtuzumab ozogamicin)

Purpose

This trial studies the side effects and how well liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin work in treating participants with acute myeloid leukemia that has come back or that does not respond to treatment or high risk myelodysplastic syndrome. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety of liposome -encapsulated daunorubicin-cytarabine (liposomal
      cytarabine and daunorubicin [CPX-351]) in combination with gemtuzumab ozogamicin (GO) in
      relapsed refractory (R-R) patients with acute myeloid leukemia (AML) and post-hypomethylating
      agent (post-HMA) failure high-risk myelodysplastic syndrome (HR-MDS).

      II. To determine the efficacy of liposomal cytarabine and daunorubicin (CPX-351) in
      combination with gemtuzumab ozogamicin (GO) in relapsed refractory patients with acute
      myeloid leukemia (AML) and post-hypomethylating agent (post-HMA) failure high-risk
      myelodysplastic syndrome (HR-MDS).

      SECONDARY OBJECTIVES:

      I. To determine the preliminary assessment of efficacy by response to revised International
      Working Group (IWG) criteria and time to response variables including overall survival (OS),
      event-free survival (EFS) and duration of response (DOR) of patients treated with this
      combination.

      EXPLORATORY OBJECTIVES:

      I. To determine the minimal residual disease (MRD) after treatment with this combination and
      its impact in long-term outcome.

      II. To determine the effect of the level of pre-treatment expression of CD33 with response to
      this combination.

      III. To determine the effect of this treatment combination on responding patients
      transitioning to hematopoietic stem cell transplantation (HSCT).

      IV. To evaluate the effect of the treatment combination on Health Related Quality of Life
      (HRQoL) parameters.

      OUTLINE:

      INDUCTION CYCLE: Participants receive liposome-encapsulated daunorubicin-cytarabine
      intravenously (IV) over 90 minutes on days 1, 3, and 5 or course and days 1 and 3 of course 2
      and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for
      up to 2 courses in the absence of unacceptable toxicity.

      CONSOLIDATION CYCLE: Participants receive liposome-encapsulated daunorubicin-cytarabine IV
      over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1.
      Treatment repeats every 28 days for up to 2 courses in the absence of unacceptable toxicity.

      MAINTENANCE CYCLE: Participants receive gemtuzumab ozogamicin IV over 120 minutes on day 1.
      Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, participants are followed up for 14 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CPX-351, gemtuzumab ozogamicin)ExperimentalINDUCTION CYCLE: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 or course and days 1 and 3 of course 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 courses in the absence of unacceptable toxicity. CONSOLIDATION CYCLE: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 courses in the absence of unacceptable toxicity. MAINTENANCE CYCLE: Participants receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Gemtuzumab Ozogamicin
  • Liposome-encapsulated Daunorubicin-Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of CD33 positive (>= 3%), relapsed refractory acute myeloid leukemia by
             World Health Organization (WHO) criteria. Patients with post-hypomethylating agent
             (post-HMA) failure high-risk myelodysplastic syndrome (MDS), as defined by the
             presence of > 10% blasts, are also eligible.

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2.

          -  Total serum bilirubin =< 2 x upper limit of normal (ULN). Patients with known
             Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN.

          -  Serum creatinine =< 2.0 mg/dl.

          -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x ULN; =<
             5 x ULN in case of suspected leukemic liver involvement.

          -  Females of childbearing potential must have a negative serum or urine beta human
             chorionic gonadotropin (b-HCG) pregnancy test result within 14 days prior to the first
             dose of study drugs and must agree to use one of the following effective contraception
             methods during the study and for 30 days following the last dose of study drug.
             Effective methods of birth control include: Birth control pills, shots, implants
             (placed under the skin by a health care provider) or patches (placed on the skin);
             Intrauterine devices (IUDs); Condom or occlusive cap (diaphragm or cervical/vault
             caps) used with spermicide; Abstinence.

          -  Females of non-childbearing potential are those who are postmenopausal greater than 1
             year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy.

          -  Males who have partners of childbearing potential must agree to use an effective
             contraceptive method during the study and for 30 days following the last dose of study
             drug.

          -  Patients or their legally authorized representative must provide written informed
             consent.

        Exclusion Criteria:

          -  History of another primary invasive malignancy that has not been definitively treated
             and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ
             are eligible regardless of the time from diagnosis (including concomitant diagnoses).

          -  Presence of clinically significant uncontrolled central nervous system (CNS) pathology
             such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain
             injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,
             or psychosis.

          -  Evidence of active cerebral/meningeal disease. Patients may have history of CNS
             leukemic involvement if definitively treated with prior therapy and no evidence of
             active disease at the time of consent with at least 2 consecutive spinal fluid
             negative assessments for residual leukemia and negative imaging (imaging required only
             if previously showing evidence of CNS leukemia not otherwise documented by spinal
             fluid assessment).

          -  Patients with active unstable angina, concomitant clinically significant active
             arrhythmias, myocardial infarction within 6 months, or congestive heart failure New
             York Heart Association class III-IV. Patients with a cardiac ejection fraction (as
             measured by either multigated acquisition scan [MUGA] or echocardiogram) < 50% are
             excluded.

          -  Patients with total cumulative doses of non-liposomal daunorubicin, or other
             anthracycline equivalent, greater than 200 mg/m^2.

          -  Patients with uncontrolled, active infections (viral, bacterial, or fungal).

          -  Known active hepatitis B or C infection, or known seropositivity for human
             immunodeficiency virus (HIV).

          -  Patients with liver cirrhosis or other serious active liver disease or with suspected
             active alcohol abuse.

          -  Allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months before the
             start of protocol-specified therapy, or with active acute/chronic graft-versus-host
             disease (GvHD) requiring systemic treatment; or receiving immunosuppression for GvHD
             prophylaxis within 2 weeks from the start of study therapy.

          -  Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the
             start of study drugs with the following exception: To reduce the circulating blast
             count or palliation; Single dose intravenous cytarabine or hydroxyurea. No washout
             necessary for these agents

          -  Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of
             all previous therapy prior to enrollment.

          -  Females who are pregnant or lactating.

          -  Male or female subjects of childbearing potential, unwilling to use an approved,
             effective means of contraception in accordance with institution's standards.

          -  Other severe, uncontrolled acute or chronic medical or psychiatric condition or
             laboratory abnormality that in the opinion of the investigator may increase the risk
             associated with study participation or investigational product administration or may
             interfere with the interpretation of study results and/or would make the patient
             inappropriate for enrollment into this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 56 days
Safety Issue:
Description:Will use the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia and Myelodysplasia.

Secondary Outcome Measures

Measure:Response and patient's clinical characteristics
Time Frame:Up to 14 months
Safety Issue:
Description:Will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate (Responders vs Non-Responders). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Measure:Event-free survival
Time Frame:Up to 14 months
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measure:Overall survival
Time Frame:Up to 14 months
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated