Study of CPX-351 (VYXEOS) in Individuals < 22 Years With Secondary Myeloid Neoplasms

NCT05656248 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: CPXSMNNCI-2022-10271
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn the effects of treatment with an investigational drug, CPX-351 in patients with secondary myeloid neoplasms (SMNs).

Conditions

Myeloid Neoplasm

Keywords

Acute myeloid leukemia (AML); Myelodysplastic syndrome (MDS); Chronic myelomonocytic leukemia (CMML)]

Outcome Measures

Primary Outcomes (3)

• Composite complete remission (CR) rates after one or two courses of CPX-351

  The Simon's two-stage minimax design with be used. Complete morphologic remission response (CR) is defined as less than 5% blasts without Auer rods by morphological evaluation of the bone marrow (M1 marrow).

  After one or 2 course of CPX-351, no later than day 42 from the start of each course of chemotherapy

• Complete remission with incomplete peripheral blood recovery (CRi) rates after one or two courses of CPX-351

  The Simon's two-stage minimax design with be used. Complete remission with incomplete peripheral blood recovery (CRi) is defined as hematologic recovery hematological (white cell blood count ≥ 1.0 x 109/L, unsupported platelet count ≥ 30.0 x 109/L and absolute neutrophil count ≥ 0.3 x 109/L).

  After one or 2 course of CPX-351, no later than day 42 from the start of each course of chemotherapy

• Safety and tolerability in patients under 22 years of age with SMN treated with one or two courses of CPX-351 before HSCT

  The exact three-stage binomial design will be used to monitor tolerability. We define a tolerability success as a patient completing two courses of therapy without experiencing a grade 4 or 5 non-hematologic toxicity.

  After one or 2 course of CPX-351, prior to hematopoietic stem cell transplantation (HSCT), three to four weeks from the hematologic recovery

Secondary Outcomes (5)

• Toxicity profile of patients with SMN treated with one or two courses of CPX-351

  30 days after completion of one or two courses of chemotherapy

• Biologic correlates of response in patients with SMN after one or two courses of CPX-351

  Day 22 for the first cycle and day 36-42 after the second cycle

• Overall (OS) survival of patients who received one or two courses of CPX-351 followed by HSCT

  3 years from study entry

• Event-free survival (EFS) of patients who received one or two courses of CPX-351 followed by HSCT

  3 years from study entry

• The impact of transplant on patients who received one or two courses of CPX-351 followed by HSCT

  3 years from study entry

Study Arms (1)

CPX-351

EXPERIMENTAL

Participants will receive CPX-351 for remission induction, and then will proceed to allogeneic HSCT or other therapies as per institutional practice. Intrathecal (IT) chemotherapy will be given on Day 1 of each cycle, for all participants, but may be delayed if clinically indicated. IT cytarabine, IT methotrexate, and IT methotrexate/hydrocortisone/cytarabine (MHA) according to age are all acceptable.

Drug: CPX-351; Drug: MHA; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

MHA DRUG

Given Intrathecal (IT)

Also known as: methotrexate/hydrocortisone/cytarabine

CPX-351

CPX-351 DRUG

Given Intraveneously (IV)

Also known as: Vyxeos®, cytarabine/daunorubicin liposomal

CPX-351

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: HSCT, Stem Cell Transplantation

CPX-351

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥1 year and \< 22 years of age at the time of enrollment.
• Patient must have one of the following diagnoses:
• Treatment-related MDS/AML: Patients with solid organ or hematopoietic neoplasms previously treated with alkylating agents, ionizing radiation, topoisomerase inhibitors, antimetabolites, thiopurines, mycophenolate mofetil, fludarabine, and anti-tubulin agents (vincristine, vinblastine, vindesine, paclitaxel, and docetaxel usually in combination), who develop MDS, or AML are candidates for the CPXSMN protocol. If the bone marrow has between 5% and 20% blasts (higher-risk MDS), patients are discussed with the hematopoietic stem cell transplantation (HSCT) team for consideration to receive chemotherapy before HSCT. If the consensus is that cytoreduction before HSCT is necessary, and the cumulative dose of doxorubicin equivalent is \< 500 mg/m2 (in cases of cardio protection) or ≤400 mg/m\^2 (cases without cardio protection), patients are eligible for the CPXSMN protocol OR
• Secondary MDS/AML: Patients with primary MDS in transformation to AML (refractory cytopenia with an excess of blasts), acquired aplastic anemia evolving to AML, myeloid neoplasms arising from inherited bone marrow failure syndromes (including severe congenital neutropenia, Schwachman-Diamond syndrome, MECOM syndrome) or MDS/AML predisposition syndromes (including germline predisposition in GATA2, RUNX1, SAMD9/SAMD9L, ERCC6L2, NF1, ETV6, ANKRD26, ERCC6L2, TP53 or CEBPA genes) are eligible for the CPXSMN trial. If the bone marrow has between 5% and 20% blasts (higher-risk MDS), patients are discussed with the HSCT team for consideration to receive chemotherapy before HSCT. If the consensus is that cytoreduction before HSCT is necessary, the patients are eligible for the CPXSMN protocol.
• Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2. Use Karnowski for patients \> 16 years of age and Lansky for patients ≤16 years of age.
• Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Concomitant medications restrictions
• See Section 4.2.5 or Appendix II (of protocol) for concomitant therapy restrictions for patients during treatment.
• Adequate renal function defined as:
• Creatinine clearance or radioisotope GFR \> 70 mL/min/1.73 m\^2, or
• A serum creatinine based on age/gender as follows: Age: 1 to \< 2 years; Maximum Serum Creatinine: Male 0.6, Female 0.6; Age: 2 to \< 6 years, Maximum Serum Creatinine: Male 0.8, Female 0.8; Age: 6 to \< 10 years; Maximum Serum Creatinine: Male 1, Female 1; Age: 10 to \< 13 years; Maximum Serum Creatinine: Male 1.2, Female 1.2; Age: 13 to \< 16 years; Maximum Serum Creatinine: Male 1.5, Female 1.5; Age: ≥ 16 years; Maximum Serum Creatinine: Male 1.7, Female 1.4
• Adequate liver function defined as (unless it is related to leukemic involvement):
• Direct bilirubin ≤1.5 x upper limit of normal (ULN) for age and institution. At institutions that do not obtain a direct bilirubin in patients with a normal total bilirubin, a normal total bilirubin may be used as evidence that the direct bilirubin is not \> 1.5 x the ULN.
• SGPT (ALT) ≤ 3.0 x ULN for age and institution
• Adequate cardiac function defined as:

You may not qualify if:

• Patients with de novo AML (i.e., patients eligible for St. Jude or COG frontline AML trials).
• Patients with any of the following:
• Constitutional trisomy 21 or with constitutional mosaicism of chromosome trisomy 21
• Patients with Fanconi anemia (DNA repair syndrome) or dyskeratosis congenita (telomeropathy)
• Wilson disease or other copper-related metabolic disorders
• Mixed phenotype acute leukemia
• Philadelphia chromosome-positive myeloid neoplasms (AML or CML)
• Acute promyelocytic leukemia (APL), or
• Juvenile myelomonocytic leukemia (JMML) and related RASopathy disorders in chronic phase.
• Patients who have received greater amount of doxorubicin equivalents to \<500 mg/m2 (in cases of cardio protection with dexrazoxane) or \<400mg/m2 (cases without cardio protection). For the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine doxorubicin equivalents:
• Doxorubicin (reference): 1
• Daunomycin: 0.5
• Epirubicin: 0.5
• Idarubicin: 5
• Mitoxantrone: 10

Sponsors & Collaborators

• Jazz Pharmaceuticals: collaborator
• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Juvenile

Interventions

CPX-351; Cytarabine; Daunorubicin; Methotrexate; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

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; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Raul C. Ribeiro, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Marcin Wlodarski, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 19, 2022
• Study Start: January 17, 2023
• Primary Completion: August 28, 2025
• Study Completion (Estimated): August 1, 2028
• Last Updated: February 4, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)