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 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 18-111
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate

  The estimated percentage of patients with Complete Responses (CR / total response-evaluable patients x 100). CR in AML is defined as: 1. Normal values for absolute neutrophil count (\>1000/microL), platelet count (\>100,000/microL), independence from red cell transfusion. 2. Bone marrow biopsy reveals no clusters or collections of blast cells. Extramedullary leukemia (eg, central nervous system or soft tissue involvement) must be absent. 3. Bone marrow aspiration 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 required.

  Up to six weeks

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  Up to five years

• Overall Survival (OS)

  Up to five years

Study Arms (1)

mitoxantrone + etoposide + gemtuzumab ozogamicin

EXPERIMENTAL

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

Interventions

mitoxantrone + etoposide + gemtuzumab ozogamicin DRUG

10 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

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and have the ability to provide written consent.
• Age: ≥18 and ≤75 years-old
• 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 or \>5% blasts if they have had an increase in blasts from the last bone marrow biopsy, will be based on their assessment after bone marrow aspiration and/or biopsy after initial treatment).
• Patients with myelodysplastic syndrome (MDS) based on the World Health Organization classification who have persistent disease after their treatment with an anthracycline and cytarabine (the diagnosis of persistent disease, which is defined as ≥10% blasts by morphology for this trial or \>5% blasts if they have had an increase in blasts from the last bone marrow biopsy, will be based on their assessment after bone marrow aspiration and/or biopsy after initial treatment).
• CD33 expression in ≥ 30% of leukemic blasts on the bone marrow.
• Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix I).
• 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.
• Left ventricular ejection fraction (LVEF) ≥50 %.
• 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:
• 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).
• 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.

You may not qualify if:

• Patients with a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the World Health Organization.
• Relapsed acute leukemia.
• Bi-lineage or bi-phenotypic leukemia.
• Prior use of mitoxantrone or etoposide or GO.
• Previous allogeneic hematopoietic cell transplantation.
• First induction course of acute myeloid leukemia with CPX-351.
• 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.
• Has known history of active Hepatitis B (HBsAg reactive) or Hepatitis C (detectable HCV RNA).
• Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patient may have not received any other investigational anti-neoplastic agents within 4 weeks from the start of therapy.
• 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 with better prognosis than AML.
• Women who are pregnant or breastfeeding.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease).

Sponsors & Collaborators

• Robert Redner, MD: lead
• Pfizer: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Mitoxantrone; Etoposide; Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Calicheamicins; Aminoglycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Barbara M Stadterman, MPH, MSCR, CCRP
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Redner Robert, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine - Hematology/Oncology

Model Details: Open label single arm

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: February 28, 2019
• Primary Completion: February 2, 2023
• Study Completion: December 22, 2024
• Last Updated: February 20, 2025
• Results First Posted: April 18, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)