Combining liposome-encapsulated chemotherapy with a targeted antibody for treating relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome

A Pilot Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Patients With Acute Myeloid Leukemia (AML) and Post-Hypomethylating Agent (Post-HMA) Failure High-Risk Myelodysplastic Syndrome (HR-MDS)

This study is testing a new combination of chemotherapy and targeted therapy to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia or high-risk myelodysplastic syndrome feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: gemtuzumab, chemotherapy
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT03672539 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the safety and efficacy of a combination treatment involving liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The study aims to assess how well these drugs work together to stop the growth of cancer cells and improve patient outcomes. Key objectives include evaluating overall survival, event-free survival, and the impact of minimal residual disease on long-term outcomes. The trial also explores the relationship between CD33 expression and treatment response.

Who should consider this trial

Good fit: Ideal candidates include patients with CD33 positive relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome who have experienced treatment failure.

Not a fit: Patients with non-CD33 positive leukemia or those with significant comorbidities that prevent participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat forms of leukemia and myelodysplastic syndrome.

How similar studies have performed: Other studies have shown promising results with similar combinations of chemotherapy and targeted therapies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of CD33 positive (\>= 3%), relapsed refractory acute myeloid leukemia by World Health Organization (WHO) criteria. Patients with post-hypomethylating agent (post-HMA) failure high-risk myelodysplastic syndrome (MDS), as defined by the presence of \> 10% blasts, are also eligible.
* Patients with MDS or chronic myelomonocytic leukemia (CMML) who received hypomethylating agent based-therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for MDS or CMML. The WHO classification will be used for AML.
* Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2.
* Total serum bilirubin =\< 2 x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to =\< 3 x ULN.
* Serum creatinine =\< 2.0 mg/dl.
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =\< 3 x ULN; =\< 5 x ULN in case of suspected leukemic liver involvement.
* Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug. Effective methods of birth control include: Birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; abstinence.
* Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy.
* Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug.
* Patients or their legally authorized representative must provide written informed consent.

Exclusion Criteria:

* History of another primary invasive malignancy that has not been definitively treated and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
* Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
* Evidence of active cerebral/meningeal disease. Patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment).
* Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV. Patients with a cardiac ejection fraction (as measured by either multigated acquisition scan \[MUGA\] or echocardiogram) \< 50% are excluded.
* Patients with total cumulative doses of non-liposomal daunorubicin, or other anthracycline equivalent, greater than 200 mg/m\^2.
* Patients with uncontrolled, active infections (viral, bacterial, or fungal).
* Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV).
* Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse.
* Allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months before the start of protocol-specified therapy, or with active acute/chronic graft-versus-host disease (GvHD) requiring systemic treatment; or receiving immunosuppression for GvHD prophylaxis within 2 weeks from the start of study therapy.
* Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exception: To reduce the circulating blast count or palliation; single dose intravenous cytarabine or hydroxyurea. No washout necessary for these agents.
* Patients must have recovered from acute non hematologic toxicity (to =\< grade 1) of all previous therapy prior to enrollment.
* Females who are pregnant or lactating.
* Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards.
* Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.
* Prior treatment with CPX-351 or gemtuzumab ozogamicin.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Yesid Alvarado-Valero, MD — M.D. Anderson Cancer Center
• Study coordinator: Yesid Alvarado-Valero, MD

Conditions Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; High Risk Myelodysplastic Syndrome; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia