Clinical Trials /

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

NCT04526288

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome with Excess Blasts-2
  • Myeloid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 Versus Immediate Donor Stem Cell Transplant for the Treatment of High-Grade Myeloid Cancers With Measurable Residual Disease
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RG1007476
  • SECONDARY ID: NCI-2020-05619
  • SECONDARY ID: RG1007476
  • NCT ID: NCT04526288

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome With Excess Blasts-2
  • Myeloid Neoplasm

Interventions

DrugSynonymsArms
Liposome-encapsulated Daunorubicin-CytarabineCPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, VyxeosArm B (CPX-351, alloHCT)

Purpose

This phase II trial investigates how well CPX-351 followed by donor stem cell transplant works compared with immediate donor stem cell transplant 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 a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.

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 up to 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 are followed up for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (alloHCT)Active ComparatorPatients undergo alloHCT.
    Arm B (CPX-351, alloHCT)ExperimentalPatients receive CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment may repeat for up to 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.
    • Liposome-encapsulated Daunorubicin-Cytarabine

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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, or ASXL1. This includes (but is not limited to)
                      the following genes: CBL (CDS), CSF3R (exons 14, 15, 17), EZH2 (exons 15-20),
                      FBXW7 (CDS), FGFR1 (exons 4, 11-17, partial 18), FLT3 (p.D835H), GATA1 (exons
                      2-3), GATA2 (exons 3-5), HRAS (exon 1-2), IDH1(p.R132), IDH2 (exon 4), JAK2 (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)
    
              -  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
    
            Exclusion Criteria:
    
              -  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
    
              -  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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall survival
    Time Frame:Up to 1 year post-randomization
    Safety Issue:
    Description:The survival (in days) of subjects in the two arms will be compared using the log-rank test.

    Secondary Outcome Measures

    Measure:Relapse-free survival
    Time Frame:From the time of minimal residual disease (MRD) identification and (among patients transplanted) from the time of transplantation up to 5 years post-randomization
    Safety Issue:
    Description:The following comparisons will be made: (1) number of days elapsing between the date of 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.
    Measure:Rate of transplantation
    Time Frame:Up to 5 years post-randomization
    Safety Issue:
    Description:The proportion of patients having begun transplant conditioning 60 days and 180 days following enrollment will be compared using the chi-squared test. The time to transplant among the two arms will be compared by comparing the number of days elapsed between enrollment and the initiation of transplant conditions by the log-rank test.
    Measure:Frequencies of the types of transplant received
    Time Frame:Up to 5 years post-randomization
    Safety Issue:
    Description:Among the patients receiving transplantation, the proportion of patients in each arm receiving myeloablative transplant 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.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Fred Hutchinson Cancer Research Center

    Last Updated

    August 21, 2020