Phase 2
N=66
Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine & Mitoxantrone for Untreated AML & High-Grade Myeloid Neoplasm
Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT03531918 ↗Enrolled (actual)
66
Serious AEs
16.7%
Results posted
Nov 2022
Primary outcome: Primary: Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1) — NA; NA Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cladribine (Drug); Cytarabine (Drug); Gemtuzumab Ozogamicin (Drug); Recombinant Granulocyte Colony-Stimulating Factor (Biological); Laboratory Biomarker Analysis (Other); Mitoxantrone Hydrochloride (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Jul 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1) |
NA; NA | — |
| PRIMARY Event-free Survival (EFS) Rate (Phase 2) |
73; 58 | — |
| SECONDARY 30-day All-cause Mortality |
.03 | — |
| SECONDARY Relapse-free Survival of GO3 Cohort |
51 | — |
| SECONDARY Overall Survival |
60 | — |
| SECONDARY Measurable Residual Disease (MRD) Rates and Remission Rates: CR |
4; 38; 0; 7 | — |
| SECONDARY Measurable Residual Disease (MRD) and Remission Rates: CRi (MRDneg) |
1; 7 | — |
| SECONDARY Measurable Residual Disease (MRD) and Remission Rates: CR/CRi |
5; 52 | — |
| SECONDARY Measurable Residual Disease (MRD) and Remission Rates: MLFS (MRDneg) |
0; 2 | — |
| SECONDARY Measurable Residual Disease (MRD) and Remission Rates: Alapasia (MRDneg) |
0; 2 | — |
Summary
This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony stimulating factor (G-CSF), cladribine, cytarabine and mitoxantrone (GCLAM) and to see how well they work in treating participants with acute myeloid leukemia or high-grade myeloid tumors (neoplasms) that have not been previously treated. Antibody-drug conjugates, such as gemtuzumab ozogamicin, act by directly delivering toxic chemotherapy to cancer cells. Granulocyte colony stimulating factor is a growth factor used to stimulate leukemia cells and render them more sensitive to chemotherapy drugs. Drugs used in chemotherapy, such as cladribine, cytarabine and mitoxantrone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gemtuzumab ozogamicin in combination with G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride may work better in treating participants with acute myeloid leukemia or high-grade myeloid neoplasm.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of untreated "high-grade" myeloid neoplasm (≥ 10% blasts in blood or bone marrow) or acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered; diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate
- Medically fit, as defined by treatment-related mortality (TRM) score ≤13.1 calculated with simplified model
- The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment
- Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow)
- Bilirubin ≤ 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)
- Serum creatinine ≤ 2.0 mg/dL (assessed within 14 days prior to study day 0)
- Left ventricular ejection fraction ≥ 45%, assessed within 12 months prior to study day 0, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure
- Women of childbearing potential and men must agree to use adequate contraception
- Provide written informed consent
Exclusion Criteria
- Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
- Concomitant illness associated with a likely survival of < 1 year
- Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials, and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. known chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible
- Known hypersensitivity to any study drug
- Confirmed or suspected pregnancy or active breast feeding
- Treatment with any other investigational anti-leukemia agent; in phase 2, treatment with a tyrosine kinase inhibitor for patients with FLT3-mutated AML is permissible
Data sourced from ClinicalTrials.gov (NCT03531918). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.