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

Last updated date
Study Location
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Contact
412-623-3083

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Myeloid Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-75 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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).

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Advanced Information
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open label single arm
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE 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.
Study Arms  ICMJE 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
Intervention: Drug: mitoxantrone + etoposide + gemtuzumab ozogamicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 12, 2019)
53
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 10, 2023
Estimated Primary Completion Date October 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathleen O'connell, RN412-623-3083[email protected]
Contact: Linda Fukas, RN412-623-6037[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03839446
Other Study ID Numbers  ICMJE HCC 18-111
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Boyiadzis, University of Pittsburgh
Study Sponsor  ICMJE Michael Boyiadzis
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Michael Boyiadzis, MDUPMC Hillman Cancer Center
PRS Account University of Pittsburgh
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP