Clinical trial NCT05558124: CPX-351 in Combination With Gemtuzumab Ozogamicin in Newly Diagnosed AML
Official title: A Phase 1/1b Dose Escalation and Expansion of CPX-351 in Combination With Gemtuzumab Ozogamicin in Newly Diagnosed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Jazz Pharmaceuticals
First posted: 2022-09-28
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine the safety of combining the drugs gemtuzumab ozogamicin (GO) with CPX-351 in order to treat the disease, as well as to find the maximum tolerated dose level and recommended Phase 2 dose level of GO with a fixed dose of CPX-351.


Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Male or female, aged ≥18 and ≤70 years with newly diagnosed any risk AML as defined by ELN 2017 criteria
* For females of child-bearing potential: use of highly effective contraception upon enrollment and during study participation and for an additional 6 months after the end of CPX-351 and Gemtuzumab ozogamicin administration: A female of child-bearing potential is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months
* The effects of CPX-351 and gemtuzumab ozogamicin on the developing human fetus are unknown. For this reason, women of child-bearing potential as defined above must have a negative serum or urine pregnancy test within 24 hours prior to beginning study treatment.
* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
* Myeloblasts expressing CD33 as determined by flow cytometry or immunohistochemistry
* ECOG ≤ 2 and eligible to receive intensive chemotherapy as determined by the treating physician
* Prior malignancy is allowed providing it does not require concurrent therapy. Exception: Active hormonal therapy is allowed.
* Prior hypomethylating agents (HMA) therapy including azacitidine or decitabine when used for non-AML diagnoses is allowed. Most recent dose must have been ≥14 days prior to day 1 of study treatment.
* Participants must have acceptable organ function
* Adequate cardiac function defined as ejection fraction of ≥50% as determined by multigated acquisition scan (MUGA) or 2D echocardiogram.
* Hydroxyurea is allowed for cytoreduction until day 1 of study treatment

Exclusion Criteria:

* Prior treatment of AML except hydroxyurea and/or leukapheresis
* Participants with acute promyelocytic leukemia (APL).
* Known current and clinically active central nervous system (CNS) leukemia.
* Severe liver disease (cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis) or patients with known Wilson's disease.
* Participants with known active infection with hepatitis B or hepatitis C virus
* Known allergic reactions to components of the CPX-351 (cytarabine or daunorubicin) or Gemtuzumab ozogamicin.
* Patients with any prior anthracycline exposure plus any planned on-study anthracycline exposure cannot not exceed 550 mg/m2 of daunorubicin (or equivalent). For participants who have received radiation therapy to the mediastinum, the total cumulative dose of anthracycline should not exceed 400 mg/m2 of daunorubicin(or equivalent).
* Hemodynamically unstable (subjects requiring vasopressor support will not be eligible).
* Treatment with another investigational drug within 14 days.
* Uncontrolled cardiac disease including congestive heart failure class III or IV by the NYHA, unstable angina (angina symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
* Any disorder that compromises the subject's ability to give written informed consent and/or to comply with study procedures.
* Any substance abuse, severe and/or uncontrolled medical, social or psychiatric conditions that may prevent the subject from completing the study, interfere with the evaluation of safety and/or efficacy, or interfere with the interpretation of the study results.
* Female subject who is pregnant or breastfeeding.
* Any patient with a known FLT3 ITD or FLT3 TKD mutation

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 18 Months
Secondary outcomes:
measure: Rate of Complete Remission
timeFrame: Up to 18 Months
measure: Measurable Residual Disease
timeFrame: Up to 18 Months
measure: Overall Survival
timeFrame: Up to 5 years
measure: Relapse Free Survival (RFS)
timeFrame: Up to 18 Months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
Study officials:
affiliation: Moffitt Cancer Center
name: Onyee Chan, MD
role: PRINCIPAL_INVESTIGATOR
References: