PRIMARY OBJECTIVES:
I. To determine the phase II dose of the combination liposome-encapsulated
daunorubicin-cytarabine (CPX-351) plus gemtuzumab ozogamicin (GO) by means of estimating
maximum tolerated dose (MTD) in participants with relapsed acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To estimate the remission rate (complete remission plus complete remission with incomplete
hematologic recovery) of participants in the MTD cohort who receive CPX-351 plus GO.
II. To evaluate CPX-351 plus GO as a bridge to allogeneic hematopoietic stem cell
transplantation (HSCT) in participants with relapsed AML.
III. To estimate the duration of remission. IV. To evaluate for toxicity by means of Common
Terminology Criteria for Adverse Events (CTCAE) version 4.03.
V. To evaluate for the development of veno-occlusive disease at any point during the study in
participants treated with CPX-351 plus GO.
VI. To evaluate time to return of normal hematopoiesis after induction therapy. VII. To
evaluate 30- and 60-day survival.
EXPLORATORY OBJECTIVES:
I. To evaluate if there is a difference in remission rate based on CD33 splicing single
nucleotide polymorphism (SNP) genotype (CC, TC, or TT) in participants receiving CPX-351 plus
GO.
II. To evaluate the impact that leukemia cell multidrug resistance activity have on achieving
remission after treatment with CPX-351 plus GO.
III. To evaluate the possible associations of participant constitutional genotype, leukemia
genotype, and response to therapy.
IV. To evaluate the possible associations of participant ribonucleic acid (RNA) expression,
leukemia RNA expression, and response to therapy.
OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin when given in combination
with liposome-encapsulated daunorubicin-cytarabine.
INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV)
over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 7 in
the first cohort of study participants, days 4 and 7 in the second cohort of study
participants, or days 1, 4, and 7 in the third cohort of study participants, in the absence
of disease progression or unacceptable toxicity. The dose expansion cohort will receive the
above treatment schedule that is determined to be the maximum tolerated dose.
CONSOLIDATION: Patients who achieve complete remission (CR)/CR with incomplete hematologic
recovery (CRi) receive consolidation therapy at the discretion of the treating physician
and/or proceed to allogeneic HSCT.
Inclusion Criteria:
- Bone marrow blasts >= 5% that develops after remission, no restriction on prior number
of relapses or regimens
- Eastern Cooperative Oncology Group (ECOG) 0-2
- At least a 3-month duration of remission prior to relapse
- Participants with relapse after allogeneic transplantation are included
- Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must
be discontinued at least 14 days prior to start of salvage induction
- Serum total bilirubin =< 2.0 mg/dL, unless considered due to Gilbert?s disease or
leukemia involvement
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 times the upper
limit of normal, unless considered due to leukemia involvement
- Alkaline phosphatase =< 3 times the upper limit of normal, unless considered due to
leukemia involvement
- Serum creatinine =< 2.0 mg/dL, or creatinine clearance > 40 mL/min based on
Cockcroft-Gault glomerular filtration rate (GFR)
- Ability to give full informed consent on their own
- Females of reproductive potential (postmenopausal for less than 24 consecutive months)
must have a negative pregnancy
Exclusion Criteria:
- Currently receiving targeted therapy for FLT3 (cytokine receptor tyrosine kinase class
III), IDH1, or IDH2 (isocitrate dehydrogenase, 1, 2) mutations and intent to continue
use; prior use of targeted therapy for such mutations is allowed, but agents should be
discontinued 1 week prior to enrollment
- Acute promyelocytic leukemia
- Second malignancy that would limit survival by less than 2 years
- New York Heart Association class III or VI
- Left ventricular ejection fraction < 50%
- History of coronary stent placement that requires mandatory continuation of
dual-antiplatelet therapy
- History of Wilson?s disease or other copper handling disorders
- Hypersensitivity to cytarabine, daunorubicin, or liposomal products
- Active invasive fungal infection
- Active bacterial or viral infection manifesting as fevers or hemodynamic instability
within the past 72 hours
- Lifetime cumulative daunorubicin-equivalent anthracycline dose > 368 mg/m^2
