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

NCT04526288 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1007476NCI-2020-0561910545
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

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

Keywords

Myeloid and Monocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Survival

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

  Up to 730 days post-randomization.

Secondary Outcomes (3)

• Relapse-free Survival

  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.

• Rate of Transplantation

  Up to 2 years post-randomization

• Frequencies of the Types of Transplantation Received

  Up to 2 years post-randomization

Study Arms (2)

Arm A (alloHCT)

ACTIVE COMPARATOR

Patients undergo alloHCT.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Arm B (CPX-351, alloHCT)

EXPERIMENTAL

Patients 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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Liposome-encapsulated Daunorubicin-Cytarabine

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo alloHCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, Hematopoietic stem cell (HSC), Hematopoietic stem cell transplant (HSCT), Stem Cell Transplantation, Allogeneic

Arm A (alloHCT); Arm B (CPX-351, alloHCT)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal Cytarabine (AraC)-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos, Daunorubicin and Cytarabine (Liposomal)

Arm B (CPX-351, alloHCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute

Interventions

Stem Cell Transplantation; CPX-351; Injections; Cytarabine; Daunorubicin; Liposomes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Drug Administration Routes; Drug Therapy; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials

Limitations and Caveats

Low accrual lead to early termination of the study. The single individual enrolled was randomized to the non-investigational arm of the study (Arm A) and was removed from the study prior to conditioning which only allowed for follow-up of overall survival. Therefore, there is little to no interpretable data to report.

Results Point of Contact

• Title: Dr. Filippo Milano, Director of FHCC Cord Blood Transplant Program
• Organization: Fred Hutchinson Cancer Center

fmilano@fredhutch.org

206.667.5925

Study Officials

• Filippo Milano

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 25, 2020
• Study Start: August 9, 2021
• Primary Completion: August 27, 2023
• Study Completion: August 27, 2023
• Last Updated: May 23, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)