Clinical Trials /

CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia

NCT03904251

Description:

This phase Ib trial studies the best dose of gemtuzumab ozogamicin when given together with CPX-351 in treating patients with acute myeloid leukemia that has come back after it was previously in remission. CPX-351 is a chemotherapy, which works in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to chemotherapy called calicheamicin. Gemtuzumab attaches to CD33 (transmembrane receptor) positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving CPX-351 and gemtuzumab ozogamicin may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia
  • Official Title: A Phase Ib Trial With Dose Expansion Evaluating CPX-351 Plus Gemtuzumab Ozogamicin for Relapsed Acute Myelogenous Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 18-001419
  • SECONDARY ID: NCI-2019-00701
  • SECONDARY ID: 18-001419
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03904251

Conditions

  • Blasts 5 Percent or More of Bone Marrow Nucleated Cells
  • Recurrent 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 phase Ib trial studies the best dose of gemtuzumab ozogamicin when given together with CPX-351 in treating patients with acute myeloid leukemia that has come back after it was previously in remission. CPX-351 is a chemotherapy, which works in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to chemotherapy called calicheamicin. Gemtuzumab attaches to CD33 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving CPX-351 and gemtuzumab ozogamicin may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the phase II dose of the combination liposome-encapsulated
      daunorubicin-cytarabine (CPX-351) plus gemtuzumab ozogamicin (GO) by means of estimating
      maximum tolerated dose (MTD) in participants with relapsed acute myeloid leukemia (AML).

      SECONDARY OBJECTIVES:

      I. To estimate the remission rate (complete remission plus complete remission with incomplete
      hematologic recovery) of participants in the MTD cohort who receive CPX-351 plus GO.

      II. To evaluate CPX-351 plus GO as a bridge to allogeneic hematopoietic stem cell
      transplantation (HSCT) in participants with relapsed AML.

      III. To estimate the duration of remission. IV. To evaluate for toxicity by means of Common
      Terminology Criteria for Adverse Events (CTCAE) version 4.03.

      V. To evaluate for the development of veno-occlusive disease at any point during the study in
      participants treated with CPX-351 plus GO.

      VI. To evaluate time to return of normal hematopoiesis after induction therapy. VII. To
      evaluate 30- and 60-day survival.

      EXPLORATORY OBJECTIVES:

      I. To evaluate if there is a difference in remission rate based on CD33 splicing single
      nucleotide polymorphism (SNP) genotype (CC, TC, or TT) in participants receiving CPX-351 plus
      GO.

      II. To evaluate the impact that leukemia cell multidrug resistance activity have on achieving
      remission after treatment with CPX-351 plus GO.

      III. To evaluate the possible associations of participant constitutional genotype, leukemia
      genotype, and response to therapy.

      IV. To evaluate the possible associations of participant ribonucleic acid (RNA) expression,
      leukemia RNA expression, and response to therapy.

      OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin when given in combionation
      with liposome-encapsulated daunorubicin-cytarabine.

      INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV)
      over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 7 in
      the first cohort of study participants, days 4 and 7 in the second cohort of study
      participants, or days 1, 4, and 7 in the third cohort of study participants, in the absence
      of disease progression or unacceptable toxicity. The dose expansion cohort will receive the
      above treatment schedule that is determined to be the maximum tolerated dose.

      CONSOLIDATION: Patients who achieve complete remission (CR)/CR with incomplete hematologic
      recovery (CRi) receive consolidation therapy at the discretion of the treating physician
      and/or proceed to allogeneic HSCT.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CPX-351, gemtuzumab ozogamicin)ExperimentalINDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 7, days 4 and 7, or days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.
  • Gemtuzumab Ozogamicin
  • Liposome-encapsulated Daunorubicin-Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Bone marrow blasts >= 5% that develops after remission, no restriction on prior number
             of relapses or regimens

          -  Eastern Cooperative Oncology Group (ECOG) 0-2

          -  At least a 3-month duration of remission prior to relapse

          -  Participants with relapse after allogeneic transplantation are included

          -  Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must
             be discontinued at least 14 days prior to start of salvage induction

          -  Serum total bilirubin =< 2.0 mg/dL, unless considered due to Gilbert?s disease or
             leukemia involvement

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 times the upper
             limit of normal, unless considered due to leukemia involvement

          -  Alkaline phosphatase =< 3 times the upper limit of normal, unless considered due to
             leukemia involvement

          -  Serum creatinine =< 2.0 mg/dL, or creatinine clearance > 40 mL/min based on
             Cockcroft-Gault glomerular filtration rate (GFR)

          -  Ability to give full informed consent on their own

          -  Females of reproductive potential (postmenopausal for less than 24 consecutive months)
             must have a negative pregnancy

        Exclusion Criteria:

          -  Currently receiving targeted therapy for FLT3, IDH1, or IDH2 mutations and intent to
             continue use; prior use of targeted therapy for such mutations is allowed, but agents
             should be discontinued 1 week prior to enrollment

          -  Acute promyelocytic leukemia

          -  Second malignancy that would limit survival by less than 2 years

          -  New York Heart Association class III or VI

          -  Left ventricular ejection fraction < 50%

          -  History of coronary stent placement that requires mandatory continuation of
             dual-antiplatelet therapy

          -  History of Wilson?s disease or other copper handling disorders

          -  Hypersensitivity to cytarabine, daunorubicin, or liposomal products

          -  Active invasive fungal infection

          -  Active bacterial or viral infection manifesting as fevers or hemodynamic instability
             within the past 72 hours

          -  Lifetime cumulative daunorubicin-equivalent anthracycline dose > 368 mg/m^2
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:Up to day 42
Safety Issue:
Description:MTD is defined as the cohort of participants one cohort below the cohort that develop dose-limiting toxicity (DLT) in at least 2 participants.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to day 42
Safety Issue:
Description:Objective response, including complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi), after induction therapy will be measured using the International Working Group (IWG) Response Criteria in acute myeloid leukemia (AML).
Measure:Proportion of participants who go on to receive allogeneic hematopoietic cell transplantation (HSCT) after achieving CR/CRi
Time Frame:Up to 18 months
Safety Issue:
Description:The proportion of patients who receive an allogeneic HSCT following a CR/CRi response will be reported along with an exact 95% confidence interval.
Measure:Duration of remission
Time Frame:Up to 18 months
Safety Issue:
Description:Evaluated in participants that achieve CR/CRi, and defined as number of days that elapse from first day CR/CRi to the first day that bone marrow blasts >= 5%. The median duration of remission will be reported in patients who achieved CR/CRi, along with the corresponding range.
Measure:Incidence of toxicities
Time Frame:Up to day 42
Safety Issue:
Description:Measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measure:Diagnosis of veno-occlusive disease (VOD)
Time Frame:Up to 18 months
Safety Issue:
Description:The diagnosis of veno-occlusive disease is based on the Baltimore criteria: Bilirubin > 2.0 mg/dL, plus, painful hepatomegaly, ascites, and weight gain > 5% basal since initiating therapy with gemtuzumab ozogamicin (GO). The proportion of patients who develop VOD will be reported along with an exact 95% confidence interval.
Measure:Time to return of normal hematopoiesis
Time Frame:From day 1 of induction, assessed up to 18 months
Safety Issue:
Description:Defined as the number of days from day 1 of induction to ANC >= 1000/uL and platelet count >= 100,000/uL. Will be reported along with the corresponding range.
Measure:Mortality
Time Frame:At 30 and 60 days following the start of induction
Safety Issue:
Description:Mortality is defined as death having occurred in any participant that receives at least one dose of experimental therapy. Kaplan-Meier methods will estimate the overall survival at day 30 and day 60 following the start of induction. The survival estimate at these two time points will be reported along with a 95% confidence interval.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

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