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) CPX-351 PLUS GEMTUZUMAB OZOGAMICIN

What's the purpose of this trial?

This phase II trial studies the side effects and how well liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin work in treating patients with acute myeloid leukemia that has come back (relapsed) or that does not respond to treatment (refractory) or high risk myelodysplastic syndrome. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine, 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. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to a toxic agent called calicheamicin. Gemtuzumab ozogamicin attached to CD33 positive cancer cells in a targeted way and delivers calicheamicin to kill them. Giving liposome-encapsulated daunorubicin-cytarabine and gemtuzumab ozogamicin together may be an effective treatment for relapsed or refractory acute myeloid leukemia or high risk myelodysplastic syndrome.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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.

Additional Trial Information

Phase 2

Enrollment: 50 patients (estimated)

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Published Results

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

December 05, 2020

Twenty pts have been enrolled between November 2018 and July 2019. At the time of data cut off 19 pts were evaluable for response, with one patient too early to assess for response. Patient characteristics are summarized on Table 1; of note 14 (70%) pts had previously been treated with venetoclax in different combinations with HMA’s and/or chemotherapy. We observed an overall response rate (ORR) of 42% (n=8), including CR (n=5), CRi (n=1) and PR (n=2). Responses are summarized in Table 2. Among the eight responders there were 4 pts with MRD negative (by flow cytometry) remission. One patient who was considered in CR was taken off study on day 40 because of an underlying invasive fungal sinus infection and concerns of myelosuppression. This patient was transitioned to a lower intensity regimen and remains in remission. Four pts completed 2 inductions, 5 pts received consolidation and 2 pts received GO maintenance before progressing. Unfortunately, none could be transitioned to transplantation due to age or comorbidities. Among responders, median time to ANC >500 was 39 days (30-56) and PLT >50k was 40 days (33-46), median time to ANC >1K was 40 days (31-74) and PLT >100K was 43 days (34-53) after induction (Table 3). With a median follow up of 18.6 months, median OS is 9.1 months (Figure 1) and median duration of response was 10.5 months (figure 2). Adverse events regardless of causality (Table 4) were mainly due to infectious complications. We have not observed treatment related grade 3-4 non-hematological toxicity. Thirty-day mortality was 10% (n=2); both pts died from complications of septicemia. Three additional pts (15%) died within 60 days of treatment, including 2 pts with progressive disease and 1 patient on day 58 after withdrawing care due to infections and 2 aplastic bone marrow examinations on days 14 and 46 of treatment, respectively.

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MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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