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Acute Myeloid LeukemiaPhase 2NCT04526288

CPX-351 Versus Immediate Stem Cell Transplantation for the Treatment of High-Grade Myeloid Cancers With Measurable Residual Disease

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation and Liposome-encapsulated Daunorubicin-Cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome With Excess Blasts-2, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

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

Official record
Search all trials

Trial summary

This phase II trial studies the effect of CPX-351 followed by donor stem cell transplantation versus immediate donor stem cell transplantation in treating patients with high-grade myeloid cancers with measurable residual disease. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation and Liposome-encapsulated Daunorubicin-Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
9 Aug 2021to 27 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL), myelodysplastic syndrome with excess blasts-2 (MDS-EB2), or another high-risk myeloid neoplasm (>= 10% blasts in the blood or marrow), having completed at least one cycle of chemotherapy intended to induce remission
  • Subjects must have MRD, defined as the presence of original disease detected by multi-parameter flow cytometry and cytogenetic/molecular assessment within 90 days of chemotherapy intended to induce remission:
  • Abnormal cells identified by multiparameter flow cytometry, present at a frequency of between 0% and 5% of total nucleated cells, judged in the opinion of the hematopathologist to represent continued presence of malignant cells
  • Abnormal karyotype; present in any number of metaphase cells
  • Abnormal fluorescence in-situ hybridization; judged in the opinion of the hematopathologist to represent continued presence of malignant cells
  • The presence of any leukemia associated mutation as detected by DNA sequencing, except mutations in DNMT3A, TET2 (tet methylcytosine dioxygenase 2), or ASXL1. This includes (but is not limited to) the following genes: CBL (CDS), CSF3R (colony stimulation factor 3 receptor; exons 14, 15, 17), EZH2 (exons 15-20), FBXW7 (CDS), FGFR1 (exons 4, 11-17, partial 18), FLT3 (FMS-like tyrosine kinase 3; p.D835H), GATA1 (exons 2-3), GATA2 (exons 3-5), HRAS (exon 1-2), IDH1 (isocitrate dehydrogenase NADP+ 1; p.R132), IDH2 (exon 4), JAK2 (Janus kinase 2; exon 12, 14, 16), KIT (8-18), KMT2A (CDS), KRAS (CDS), MAP2K1 (exons 2, 3, 6), MPL (exon 10), MYD88 (exon 3-5), NOTCH1 (exons 20, 26, 27), NPM1 (exon 12), NRAS (CDS), PDGFRA (exons 12-18), PHF6 (CDS), PTEN (CDS), RB1 (CDS), RUNX1 (exon 4-8), SF3B1 (exon 14-16), SRSF2 (exon 1), STAG2 (CDS), STAT3 (exons 20-21), TP53 (CDS), U2AF1 (exons 2, 6), WT1 (CDS), and ZRSR2 (CDS)
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  • Allowable prior therapy:
  • For the purposes of this study intensive chemotherapy will include regimens listed below. Additional regimens may be included at the discretion of the study principal investigator (PI)
  • Any regimen including cytarabine at a dose of 100 mg/m^2/day for at least 7 days and an anthracycline at any dose +/- gemtuzumab ozogamicin (GO)
  • Any regimen including cytarabine at a dose of at least 100 mg/m^2/day for at least 5 days and a purine analog at any dose (e.g. clofarabine, fludarabine, cladribine) +/- GO
  • Ability to understand and voluntarily sign a written informed consent document (ICF)
  • Absence of a concomitant illness with a likely survival of < 1 year
  • Medically fit, defined as a treatment related mortality score (TRM) of =< 13.1 calculated according to Walter et al, Journal of Clinical Oncology (JCO) 2011
  • Additionally, subjects should be eligible in the opinion of their treating physician for allogeneic transplantation
  • Bilirubin =< 2.5 x institutional upper limit of normal, unless elevation is thought to be due to Gilberts syndrome or hemolysis (within 14 days of study start [unless otherwise noted] to be enrolled in the study)
  • Left ventricular ejection fraction >= 40% assessed by multiple gated acquisition scan (MUGA), echocardiography or other appropriate diagnostic modality within 12 months of enrollment with no clinical evidence of decompensated congestive heart failure
  • Creatinine clearance of >= 30 mL/min as measured by Cockcroft Gault equation (within 14 days of study start [unless otherwise noted] to be enrolled in the study)
  • Consent of female patients with a negative serum or urine pregnancy test to use a medically acceptable method of contraception throughout the entire study period and for 6 months following the last dose of CPX-351
  • Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351 and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351
  • Patients enrolling in this trial should intend to complete the treatments described and should be eligible in the opinion of the treating physician for allogeneic transplantation
  • Patients must have a caregiver capable of providing post-HCT care, who will be present once conditioning therapy begins
  • The informed consent document (ICF) must be signed and dated by the subject or by the subject's legally authorized representative if the subject is unable to sign

Who cannot join

  • Allogeneic myeloablative hematopoietic cell transplant within 6 months
  • Autologous hematopoietic cell transplant within 6 months
  • Known Hypersensitivity to CPX-351
  • Patients may not have known hypersensitivity to CPX-351, daunorubicin, cytarabine, or liposomal products
  • Prior treatment with two or more cycles of CPX-351
  • Treatment within the last 30 days of other investigational antineoplastic agents
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  • Evidence of organ dysfunction likely to preclude safe transplantation including the following:
  • Symptomatic coronary artery disease or uncontrolled arrhythmia within the prior 3 months and since most recent anthracycline exposure
  • Myocardial impairment of any cause resulting in heart failure as determined by New York (NY) Heart Association Criteria (class III or IV)
  • Corrected diffusion capacity of the lung for carbon monoxide (DLCOc) < 40% or forced expiratory volume in 1 second (FEV1) < 50%
  • Need for supplemental oxygen
  • Active systemic fungal, bacterial, viral or other infection, unless under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)])
  • Female patients who are pregnant, nursing, or lactating
  • Patients with an inability to accept blood transfusions
  • Inability to give informed consent, or unable to comply with the treatment protocol including appropriate supportive care, follow-up and tests
  • Any other condition that would cause a risk to patients if they participate in the trial

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Randomized Trial for Patients With High-Grade Myeloid Neoplasms With Measurable Residual Disease (MRD): CPX-351 vs. Immediate Allogeneic Hematopoietic Cell Transplantation

This phase II trial studies the effect of CPX-351 followed by donor stem cell transplantation versus immediate donor stem cell transplantation in treating patients with high-grade myeloid cancers with measurable residual disease. Chemotherapy drugs, such as CPX-351, 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. Giving chemotherapy before donor stem cell transplantation may help kill cancer cells in the body and make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.

Read the detailed description

OUTLINE:

Patients are randomized to 1 of 2 arms.

Arm A: Patients undergo alloHCT.

Arm B: Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Treatment may repeat for an additional cycle for a total of 2 cycles (on days 1 and 3 only of cycle 2) in the absence of disease progression or unacceptable toxicity. Within 60 days after completion of CPX-351, patients undergo alloHCT.

After completion of study enrollment, patients will be followed for up to 2 years.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Liposome-encapsulated Daunorubicin-Cytarabine
Keywords
Myeloid and Monocytic Leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, Hematopoietic stem cell (HSC), Hematopoietic stem cell transplant (HSCT)

    Undergo alloHCT

  • Liposome-encapsulated Daunorubicin-CytarabineDrug

    Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal Cytarabine (AraC)-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin

    Given IV

Study groups in NCT04526288
Study groupRoleWhat they receive
Arm A (alloHCT)Active comparatorPatients undergo alloHCT.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Arm B (CPX-351, alloHCT)ExperimentalPatients receive CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment may repeat for an additional cycle for a total of 2 cycles (on days 1 and 3 only of cycle 2) in the absence of disease progression or unacceptable toxicity. Within 60 days after completion of CPX-351, patients undergo alloHCT.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Liposome-encapsulated Daunorubicin-Cytarabine

What is being measured

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

  1. Overall Survival

    The survival (in days) of subjects in the two arms will be compared using the log-rank test.

    Measured: Up to 730 days post-randomization.

Secondary outcomes (3)

  1. Relapse-free Survival

    The following comparisons will be made: (1) number of days elapsing between the date of minimal residual disease (MRD) identification and the date of death or relapse, (2) among transplanted patients, the number of days elapsing between the date of transplantation and the date of death or relapse.

    Measured: From the time of randomization up to 2 years post-randomization. For descriptive purposes, we shall also report survival and relapse-free survival from time of transplant up to 2 years post-transplant among patients who receive a transplant.

  2. Rate of Transplantation

    This outcome will be assessed among patients who have begun transplantation conditioning 60 days and 180 days following enrollment will be compared using the chi-squared test. The time to transplantation among the two arms will be compared by comparing the number of days elapsed between enrollment and the initiation of transplantation conditions by the log-rank test.

    Measured: Up to 2 years post-randomization

  3. Frequencies of the Types of Transplantation Received

    Among the patients receiving transplantation, the proportion of patients in each arm receiving myeloablative transplantation conditioning will be compared using the chi-squared or Fisher's exact test. Among patients receiving transplantation, the proportion of patients in each arm receiving donor stem cells from a haploidentical donor, an unrelated donor, or from cord blood unit will each be compared using the chi-squared or Fisher's exact test.

    Measured: Up to 2 years post-randomization

Timeline

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

  1. First posted25 Aug 2020
  2. Study start9 Aug 2021
  3. Primary completion27 Aug 2023
  4. Study completion27 Aug 2023

Why it stopped: Terminated due to low accrual

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04526288
Sponsor's protocol ID
RG1007476
Other IDs
NCI-2020-05619, 10545
Status last verified
Apr 2024
First submitted
21 Aug 2020
Last updated
23 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation and Liposome-encapsulated Daunorubicin-Cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome With Excess Blasts-2, run by Fred Hutchinson Cancer Center 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 22 inclusion and 16 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 23 May 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Survival (time frame: Up to 730 days post-randomization.). 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 NCT04526288.

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 23 May 2024.

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