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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

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ClinicalTrials.gov Identifier: NCT03839446
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : March 4, 2019
Sponsor:
Information provided by (Responsible Party):
Michael Boyiadzis, University of Pittsburgh

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: mitoxantrone + etoposide + gemtuzumab ozogamicin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open label single arm
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 28, 2019
Estimated Primary Completion Date : October 10, 2020
Estimated Study Completion Date : November 10, 2023


Arm Intervention/treatment
Experimental: mitoxantrone + etoposide + gemtuzumab ozogamicin
10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6
Drug: mitoxantrone + etoposide + gemtuzumab ozogamicin
10 mg/m2 mitoxantrone days 1-5 + 100mg/m2 etoposide days 1-5 + 3mg/m2 gemtuzumab ozogamicin on day 6.




Primary Outcome Measures :
  1. Complete Remission Rate [ Time Frame: Up to six weeks ]

    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 :
  1. Progression-free Survival (PFS) [ Time Frame: Up to five years ]
    The length of time during and after the treatment that a patient lives with Acute Myeloid Leukemia that does not get worse.

  2. Overall Survival (OS) [ Time Frame: Up to five years ]
    The length of time from the start of treatment that patients are still alive.

  3. Cytogenetic Status [ Time Frame: 1 day (Determine once, at the time of AML diagnosis) ]
    Poor, Intermediate, Favorable chromosomal status.

  4. Percent of blasts [ Time Frame: 1 day (Determined once, after treatment) ]
    Percent of blasts present in the bone marrow after therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03839446


Contacts
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Contact: Michael Boyiadzis, MD 412-623-0040 boyiadzism@upmc.edu
Contact: Carrie Muniz 412-623-6212 munizca@upmc.edu

Locations
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United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Michael Boyiadzis, MD    412-623-0040    boyiadzism@upmc.edu   
Contact: Carrie Muniz, BSN    412-623-6121    munizca@upmc.edu   
Principal Investigator: Michael Boyiadzis, MD         
Sponsors and Collaborators
Michael Boyiadzis

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Responsible Party: Michael Boyiadzis, Associate Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03839446     History of Changes
Other Study ID Numbers: HCC 18-111
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Boyiadzis, University of Pittsburgh:
cytogenetic status
mitoxantrone
etoposide
gemtuzumab ozogamicin
bone marrow

Additional relevant MeSH terms:
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Mitoxantrone
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Etoposide
Etoposide phosphate
Gemtuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antineoplastic Agents, Immunological