Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromePhase 2NCT03672539
Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome
A Phase 2 study testing Gemtuzumab Ozogamicin, Liposome-encapsulated Daunorubicin-Cytarabine and Quality-of-Life Assessment in people with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, High Risk Myelodysplastic Syndrome
- What is being tested?
- Gemtuzumab Ozogamicin, Liposome-encapsulated Daunorubicin-Cytarabine and Quality-of-Life Assessment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2018to 17 Jul 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety of liposome-encapsulated daunorubicin-cytarabine (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).
II. To determine the efficacy 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).
SECONDARY OBJECTIVE:
- To determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR) of patients treated with this combination.
EXPLORATORY OBJECTIVES:
- To determine the minimal residual disease (MRD) after treatment with this combination and its impact in long-term outcome.
II. To determine the effect of the level of pre-treatment expression of CD33 with response to this combination.
III. To determine the baseline CD33 genotype via CD33 polymorphism study, and its effect on response to this combination.
IV. To determine the effect of this treatment combination on responding patients transitioning to hematopoietic stem cell transplantation (HSCT).
- To evaluate the effect of the treatment combination on Health Related Quality of Life (HRQoL) parameters.
OUTLINE:
INDUCTION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 of cycle 1 and days 1 and 3 of cycle 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity.
CONSOLIDATION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity.
MAINTENANCE CYCLE: Patients receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 14 months.
- 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
- Being tested
- Gemtuzumab Ozogamicin, Liposome-encapsulated Daunorubicin-Cytarabine, Quality-of-Life Assessment
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemtuzumab OzogamicinDrug
Also called Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab
Given IV
Liposome-encapsulated Daunorubicin-CytarabineDrug
Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CPX-351, gemtuzumab ozogamicin) | Experimental | INDUCTION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 of cycle 1 and days 1 and 3 of cycle 2 and gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity.
CONSOLIDATION CYCLE: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and gemtuzumab ozogamicin over 120 minutes on day 1. Treatment repeats every 28 days for up to 2 cycles in the absence of unacceptable toxicity.
MAINTENANCE CYCLE: Patients receive gemtuzumab ozogamicin IV over 120 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Gemtuzumab Ozogamicin; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Will use the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia and Myelodysplasia. Will estimate the ORR for the combination treatment, along with the 95% credible interval.
Measured: Up to 56 days
Incidence and severity of all adverse events assessed using Common Toxicity Criteria version 4.0
Measured: Up to 14 months
Secondary outcomes (4)
Demographic/clinical characteristics (i.e. duration of response) and safety data of the patients
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Measured: Up to 14 months
Response and patient's clinical characteristics
Will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate (Responders vs Non-Responders). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Measured: Up to 14 months
Event-free survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measured: Up to 14 months
Overall survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measured: Up to 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2018
- Study start7 Nov 2018
- Primary completion17 Jul 2026
- Study completion17 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yesid Alvarado-Valero, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03672539
- Sponsor's protocol ID
- 2018-0235
- Other IDs
- NCI-2018-01812, 2018-0235
- Status last verified
- Jul 2026
- First submitted
- 10 Sep 2018
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alvarado Y, Senapati J, Kadia TM, Borthakur G, Montalban-Bravo G, Short NJ, Daver N, DiNardo CD, Masarova L, Ferrajoli A, Haddad FG, Jabbour E, Torralba AB, Tan S, Arora S, Pierce S, Faderl S, Garcia-Manero G, Kantarjian HM, Ravandi F. CPX-351 plus gemtuzumab ozogamicin in relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood Neoplasia. 2026 Aug 25;3(4):100292. doi: 10.1016/j.bneo.2026.100292. eCollection 2026 Nov.
PubMed 42835577