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Acute Myeloid LeukemiaPhase 1CPX GONCT03878927

CPX-351+GO in Subjects 55 Years Old, or Older, With AML

A Phase 1 study testing CPX-351 and Gemtuzumab Ozogamicin in people with Acute Myeloid Leukemia, run by Weill Medical College of Cornell University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open label study to assess the safety and efficacy of CPX-351 in combination with gemtuzumab ozogamicin (GO) as first intensive therapy in older (age >55 years) subjects with newly diagnosed AML who are eligible for intensive induction chemotherapy, or AML subjects who previously failed low-intensity… Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
CPX-351 and Gemtuzumab Ozogamicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
23 Aug 2019to 1 Sep 2022
Phase
Phase 1
Are there results?
None posted in the registry

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 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and voluntarily give informed consent
  • Age≥55 years at the time of study treatment
  • Pathological diagnosis of AML according to WHO criteria (with >20% blasts in the peripheral blood or bone marrow) including:
  • De novo AML with intermediate or adverse-risk karyotypes (including subjects with karyotypic abnormalities characteristic of MDS), who may have received treatment with low-dose cytarabine, hypomethylating agents, and/or non-intensive chemotherapy-based clinical trial treatments
  • Secondary AML: transformed from prior MDS or MPN, confirmed by bone marrow documentation of prior antecedent hematologic disorder
  • Therapy-related AML: t-AML, requires documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease
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  • Performance status >50% KPS, ECOG 0-2
  • Laboratory values fulfilling the following:
  • Peripheral blast count is less than 30,000/μL prior to administration of drug
  • Serum creatinine < 2.5 mg/dL
  • Serum total bilirubin < 2.5 mg/dL
  • Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN
  • Subjects with elevated liver enzymes and serum creatinine values secondary to AML are eligible after discussion with PI
  • Cardiac ejection fraction ≥ 50% by echocardiography, MUGA, or Cardiac MRI
  • Negative pregnancy test for non-menopausal women ≥ 55 years old
  • Subjects with history of second malignancies in remission may be eligible if there is clinical evidence of disease stability off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Subjects maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible.

Who cannot join

  • Acute promyelocytic leukemia [t(15;17)], AML with karyotype inversion 16 or t(8;21)
  • Clinical or morphologic evidence of active CNS leukemia
  • Prior intensive chemotherapy for AML with anthracycline/cytarabine-based regimens, GO or other antibody targeting CD33 as a single agent and/ or prior HSCT. Subjects may have been treated with commercially available or investigational hypomethylating agents (e.g. decitabine, azacitidine, SGI-110), lenalidomide, or low-dose cytarabine (not to exceed 20 mg/m2 daily for 14 days for ≤ 6 cycles) or on clinical trials with combinations of low-intensity chemotherapy agents. No more than one agent or combination of agents can be given for treatment of AML prior to enrollment onto this protocol.
  • Prior treatment including HMA, systemic chemotherapy, surgery, or radiation therapy must have been completed at least 7 days before start of study treatment or after discussion with PI. Treatment with investigational agents must have been completed at least 14 days prior to study drug treatment. Hydroxyurea is permitted for control of blood counts before the start of study treatment. Toxicities associated with prior therapies must have recovered to grade 1 or less prior to start of study treatment.
  • Subjects with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
  • Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
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  • Subjects with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)
  • Active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs.
  • Subjects with current or recent evidence of invasive fungal infection (blood or tissue culture); subjects with recent fungal infection must have a subsequent negative cultures to be eligible
  • Known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values)
  • Hypersensitivity to cytarabine, daunorubicin or liposomal products
  • History of Wilson's disease or other copper-metabolism disorder
  • History of prior bone marrow or solid organ transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Weill Cornell Medical College

    New York, New York, 10021

Other trials in United States

About this study

Official title: Phase I Trial, With an Expansion Cohort, of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Combination With Gemtuzumab in Subjects With Acute Myeloid Leukemia >55 Years of Age Who Have Not Been Treated With Intensive Chemotherapy

This is an open label study to assess the safety and efficacy of CPX-351 in combination with gemtuzumab ozogamicin (GO) as first intensive therapy in older (age >55 years) subjects with newly diagnosed AML who are eligible for intensive induction chemotherapy, or AML subjects who previously failed low-intensity therapy but who would be eligible for high-intensity chemotherapy, with companion cognitive function testing to determine whether this contributes to outcome in these subjects. Subjects may have received prior AML treatment with non-intensive regimens, e.g. hypomethylating agents, low-dose cytarabine, or lenalidomide or a clinical trial drug in combination with hypomethylating agents or low-dose cytarabine, but may not have received intensive AML treatment with anthracyclines and/or infusional cytarabine prior to enrollment on this trial. Subjects may not have been treated with GO or other antibody targeting CD 33 prior to enrollment on this trial. The cohort will include 30 subjects treated with the combination of CPX-351 and GO and is designed to establish the safety and feasibility of the combination. These subjects will be assessed for efficacy and safety. Quality of life will be assessed using the FACT-LEU in all subjects. Cognitive function will be assessed using the Blessed Orientation-Memory-Concentration Test and the Montreal Cognitive Assessment.

Being tested
CPX-351, Gemtuzumab Ozogamicin
Keywords
AML, De novo AML, Secondary AML, Therapy-related AML
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPX-351Drug

    Also called Vyxeos

    CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio. The liposome membrane is composed of distearoylphosphatidylcholine, distearoylphosphatidylglycerol and cholesterol in a 7:2:1 molar ratio.

  • Gemtuzumab OzogamicinDrug

    Also called Mylotarg

    Gemtuzumab ozogamicin is a CD-33 directed antibody drug conjugated to calicheamicin. CD 33 is expressed on myeloid leukemic blast cells and on normal hematopoietic cells. The drug is approved for the treatment of newly diagnosed CD 33 positive AML in adults and the treatment of relapsed and refractory CD 33 positive AML in adults. The drug is available for injection 4.5 mg as a lyophilized cake or powder in a single use vial for reconstitution and dilution.

Study groups in NCT03878927
Study groupRoleWhat they receive
Cohort AExperimentalCPX-351 : Daunorubicin 44mg/m^2 and cytarabine 100mg/m^2/day on Days 1,3 and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m^2/day on Day 1 (2 hour IV infusion)
Receives: Drug: CPX-351; Drug: Gemtuzumab Ozogamicin
Cohort BExperimentalCPX-351: Daunorubicin 44mg/m^2 and cytarabine 100mg/m^2 on Days 1, 3 and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m^2 on Days 1, 4 (2 hour IV infusion)
Receives: Drug: CPX-351
Cohort CExperimentalCPX-351: Daunorubicin 44mg/m^2 and cytarabine 100mg/m^2 on Days 1, 3, and 5 (90 minute IV infusion) Gemtuzumab ozogamicin: 3mg/m^2 on Days 1, 4 and 7 (2 hour IV infusion)
Receives: Drug: CPX-351; Drug: Gemtuzumab Ozogamicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasible dose of Gemtuzumab Ozogamicin (GO) in combination with CPX-351 (cytarabine:daunorubicin) in older subjects with AML

    The combination of CPX-351 + GO will be declared feasible if at least one dose of GO (day 1, 4, and 7) at 3 mg/m^2 can be safely delivered to subjects.

    Measured: 5 years

Secondary outcomes (8)
  1. Efficacy of the combination of CPX and GO as first intensive therapy in elderly (age ≥55 years) by response rate

    The efficacy of the combination of CPX-351 and GO in this population will be assessed by treatment response rate, as determined by bone marrow analysis at Day 14 of each induction and consolidation, and as needed thereafter, up to 5 years.

    Measured: 5 years

  2. Safety of the combination of CPX and GO in elderly (age ≥55 years) subjects with AML by evaluation of the frequency and severity of adverse events.

    The safety of CPX-351 in this population will be assessed by evaluation of the frequency and severity of adverse events.

    Measured: 5 years

  3. Assessment of Minimal Residual Disease (MRD) response in subjects treated with this combination using multiparameter flow cytometry and next generation sequencing.

    MRD is defined as posttherapy persistence of leukemia cells at levels below morphologic detection, and is a prognostic marker of increased risk of relapse and shorter survival in this subject population.

    Measured: 5 years

  4. Quality of Life Assessment using the Functional Assessment of Cancer Therapy-Leukemia (FACT-LEU).

    Leukemia Subscale (LeuS): Range:0-68. To derive: Subtract the answers from "4" for each of the 17 questions, except #s 11 and 12 (these are added without modification). Add values, multiply by 17 and divide by # of questions answered. FACT-Leu total =PWB+SWB+EWB+FWB+LeuS. Range: 0-176.

    Measured: 5 years

  5. Assessment of the relationship of cognitive function to outcome using the Blessed Orientation-Memory-Concentration Test

    The relationship of cognitive function to outcome will be assessed using the Blessed Orientation-Memory-Concentration Test. The score for 6 items are multiplied to yield a "weighted" score. The higher the total weighted score, the more likely the patient has cognitive disability. Weight scores totaling greater than 10 are generally accepted as an indication of the presence of clinically meaningful cognitive impairment.

    Measured: 5 years

  6. Assessment of the relationship of cognitive function to outcome using the Montreal Cognitive Assessment (MoCA).

    The relationship of cognitive function to outcome will be assessed using the MoCA. The MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal.

    Measured: 5 years

  7. CPX-351 as a post-remission (consolidation) therapy

    The safety of CPX-351 as a post-remission (consolidation) therapy will be assessed by evaluation of the frequency and severity of adverse events.

    Measured: 5 years

  8. Rate of morphologic leukemia-free state (MLFS)

    The rate of morphologic leukemia-free state (MLFS) will be determined to supplement the efficacy assessment of CPX-351.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2019
  2. Study start23 Aug 2019
  3. Primary completion15 Aug 2022
  4. Study completion1 Sep 2022

Why it stopped: Dose limiting toxicities.

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03878927
Sponsor's protocol ID
1801018937
Acronym
CPX GO
Status last verified
Dec 2021
First submitted
12 Mar 2019
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.

    PubMed 19880497
  • Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2004:98-117. doi: 10.1182/asheducation-2004.1.98.

    PubMed 15561679
  • Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH. Age and acute myeloid leukemia. Blood. 2006 May 1;107(9):3481-5. doi: 10.1182/blood-2005-09-3724. Epub 2006 Feb 2.

    PubMed 16455952
  • Kantarjian H, O'brien S, Cortes J, Giles F, Faderl S, Jabbour E, Garcia-Manero G, Wierda W, Pierce S, Shan J, Estey E. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006 Mar 1;106(5):1090-8. doi: 10.1002/cncr.21723.

    PubMed 16435386
  • Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. 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. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.

    PubMed 14673054

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CPX-351 and Gemtuzumab Ozogamicin in people with Acute Myeloid Leukemia, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Dose limiting toxicities.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasible dose of Gemtuzumab Ozogamicin (GO) in combination with CPX-351 (cytarabine:daunorubicin) in older subjects with AML (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03878927, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023; AzTrials last refreshed its copy on 7 Nov 2026.

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