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Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy

NCT03839446

Description:

This study is an open-label, single arm phase II study which will examine the efficacy and toxicity of the combination therapy of GO, mitoxantrone and etoposide in patients who did not respond to first line induction therapy.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy
  • Official Title: Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy

Clinical Trial IDs

  • ORG STUDY ID: HCC 18-111
  • NCT ID: NCT03839446

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
mitoxantrone + etoposide + gemtuzumab ozogamicinmitoxantrone + etoposide + gemtuzumab ozogamicin

Purpose

This study is an open-label, single arm phase II study which will examine the efficacy and toxicity of the combination therapy of GO, mitoxantrone and etoposide in patients who did not respond to first line induction therapy.

Detailed Description

      Eligible patients will be treated inpatient. Patients will receive mitoxantrone 10mg/m2
      administered intravenous piggyback (IVPB) in 50ml 0.9% normal saline over 15 minutes on days
      1-5 and etoposide 100 mg/m2 administered intravenously in 500 ml of 0.9% sodium chloride over
      2 hours on days 1-5.

      On day 6, patients will receive a single dose of GO 3mg/m2 (maximum dose 4.5mg). Patients
      will be pre-medicated 1 hour prior to the GO infusion with diphenhydramine 50mg administered
      orally or intravenously, acetaminophen 650 mg administered orally or intravenously and 1mg/kg
      methylprednisolone or an equivalent dose of alternative corticosteroid administered IV within
      30 minutes prior to infusion of GO. GO will be administered intravenously in 50 ml (or other
      suitable volume resulting in a final GO concentration between 0.075 mg/mL to 0.234 mg/mL) of
      0.9% sodium chloride over 2 hours. Doses of GO will be based on BSA calculated using actual
      body weight with a cap of 4.5mg. Vital signs will be recorded within one hour prior to the
      infusion and then every 30 minutes during the infusion and 30 minutes and one hour after
      completion of infusion. An additional dose of methylprednisolone 1 mg/kg IV may be given for
      any sign of infusion reaction, such as fever, chills, hypotension, or dyspnea occurring
      during the GO infusion or within 4 hours after the GO infusion.

      For dose modifications based on kidney and liver function please see the treatment schema at
      the end of the study.

      Supportive care including blood product transfusions, antiemetic medications, antiviral and
      antifungal medications, growth factor support, tumor lysis syndrome prophylaxis, or empiric
      antibiotics may be used at the clinical discretion of the provider.
    

Trial Arms

NameTypeDescriptionInterventions
mitoxantrone + etoposide + gemtuzumab ozogamicinExperimental10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6
  • mitoxantrone + etoposide + gemtuzumab ozogamicin

Eligibility Criteria

        Inclusion Criteria:

          1. Able to understand and have the ability to provide written consent.

          2. Age: 18 - 75 years-old.

          3. Patients with newly diagnosed AML based on the World Health Organization
             classification who have persistent disease after their first course treatment with an
             anthracycline and cytarabine (the diagnosis of persistent disease, which is defined as
             >10% blasts by morphology for this trial, will be based on their assessment after bone
             marrow aspiration and/or biopsy after initial treatment).

          4. CD33 expression in ≥ 30% of leukemic blasts on the bone marrow.

          5. Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix I).

          6. Patients must have the following laboratory values prior to beginning protocol
             treatment:

               -  Calculated creatinine clearance ≥ 30 mL/min (using the Cockcroft-Gault equation
                  CL creatinine = ((140-age) x body mass X 0.85 if female)/72 x creatinine where
                  age is given in years, body mass is given in Kg and creatinine is given in
                  mg/dl).

               -  Aspartate aminotransferase (AST) ≤ 2.5 x upper normal limit.

               -  Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit.

               -  Total bilirubin ≤ 2 x upper normal limit. Note: As many eligible patients will be
                  pancytopenic secondary to their disease or prior treatments, hematologic
                  abnormalities will not be used as criteria for entry or exclusion.

          7. Left ventricular ejection fraction (LVEF) ≥50 %.

          8. Females of child-bearing potential must have a negative pregnancy test during
             screening and all subjects must agree to use an effective method of contraception. A
             woman is eligible to enter and participate in the study if she is of:

               1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant)
                  including any female who has had a hysterectomy or has had a bilateral
                  oophorectomy (ovariectomy).

               2. Childbearing potential, has a negative serum pregnancy test during the screening
                  period and agrees to avoid sexual activity or use contraception from screening
                  through follow-up (method of birth control if the patient is not neutropenic
                  include the use of a diaphragm, intrauterine device, contraceptive sponge and/or
                  usage of male condom with a spermicide from the partner). A man with a female
                  partner of childbearing potential is eligible to enter and participate in the
                  study if he has either had a prior vasectomy or agrees to avoid sexual activity
                  or use adequate contraception (as described above) from screening through
                  follow-up.

        Exclusion Criteria:

          1. Patients with a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the
             World Health Organization.

          2. Relapsed acute leukemia.

          3. Bi-lineage or bi-phenotypic leukemia.

          4. Prior use of mitoxantrone or etoposide or GO.

          5. Previous allogeneic or autologous hematopoietic cell transplantation or solid organ
             transplantation.

          6. First induction course of acute myeloid leukemia with CPX-351.

          7. Prior use of a FLT3 inhibitor.

          8. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of treating investigator.

          9. Has known history of active Hepatitis B (HBsAg reactive) or Hepatitis C (detectable
             HCV RNA).

         10. Uncontrolled, life-threatening infection that is not responding to antimicrobial
             therapy.

         11. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         12. Patient may have not received any other investigational anti-neoplastic agents within
             4 weeks from the start of therapy.

         13. Concurrent active malignancy; exceptions include patients who have been disease free
             for 5 years, patients with a history of completely resected non-melanoma skin cancer
             or successfully treated in situ carcinoma, or patients with another malignancy that is
             indolent or definitively treated.

         14. Women who are pregnant or breastfeeding.

         15. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
             respiratory or cardiac disease).
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission Rate
Time Frame:Up to six weeks
Safety Issue:
Description:The number of patients that experience complete remission / total number of patients. Complete Remission in AML is defined as: 1. Normal values for absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL), and independence from red cell transfusion. 2. A bone marrow biopsy that reveals no clusters or collections of blast cells. Extramedullary leukemia (eg, central nervous system or soft tissue involvement) must be absent. 3. A bone marrow aspiration that reveals normal maturation of all cellular components (ie, erythrocytic, granulocytic, and megakaryocytic series). No requirement for bone marrow cellularity. 4. < 5 percent blast cells are present in the bone marrow, and none can have a leukemic phenotype (eg, Auer rods). 5. The absence of a previously detected clonal cytogenetic abnormality (ie, complete cytogenetic remission, CRc) confirms the morphologic diagnosis of CR but is not currently a required criterion.

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Up to five years
Safety Issue:
Description:The length of time during and after the treatment that a patient lives with Acute Myeloid Leukemia that does not get worse.
Measure:Overall Survival (OS)
Time Frame:Up to five years
Safety Issue:
Description:The length of time from the start of treatment that patients are still alive.
Measure:Cytogenetic Status
Time Frame:1 day (Determine once, at the time of AML diagnosis)
Safety Issue:
Description:Poor, Intermediate, Favorable chromosomal status.
Measure:Percent of blasts
Time Frame:1 day (Determined once, after treatment)
Safety Issue:
Description:Percent of blasts present in the bone marrow after therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Michael Boyiadzis

Trial Keywords

  • cytogenetic status
  • mitoxantrone
  • etoposide
  • gemtuzumab ozogamicin
  • bone marrow

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