CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients

Randomized Phase 2 Trial of CPX-351 (Vyxeos) vs. CLAG-M (Cladribine, Cytarabine, G-CSF, and Mitoxantrone) in Medically Less-Fit Adults With Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm

Sponsors

Lead Sponsor: Fred Hutchinson Cancer Research Center

Collaborator: National Cancer Institute (NCI)
Jazz Pharmaceuticals

Source Fred Hutchinson Cancer Research Center
Brief Summary

This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.

Detailed Description

OUTLINE: Patients are randomized to 1 of 2 arms in a 1:1 fashion. ARM I = CPX-351; ARM II = CLAG-M. ARM I (INDUCTION): Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. ARM I (POST-REMISSION): Patients who achieve a CR or CR with incomplete hematologic recovery (CRi) receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity. ARM II (INDUCTION): Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF subcutaneously (SC) on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. ARM II (POST-REMISSION): Patients who achieve a CR/CRi receive an intermediate dose of cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 5 years.

Overall Status Recruiting
Start Date 2020-03-11
Completion Date 2026-12-31
Primary Completion Date 2024-05-31
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
3-month overall survival (OS) Up to 3 months from date of start of protocol therapy
Secondary Outcome
Measure Time Frame
Complete remission (CR) rates Up to 5 years post treatment
MRDneg CR rates Up to 5 years post treatment
Response duration Up to 5 years post treatment
Relapse-free survival Up to 5 years post treatment
Incidence of adverse events Up to 5 years post treatment
30-day mortality rate At 30 days
60-day mortality At 60 days
Quality of life (QOL): questionnaire Up to 5 years post treatment
Patient use of medical resources (e.g. transfusions) Up to 5 years post treatment
Enrollment 60
Condition
Intervention

Intervention Type: Drug

Intervention Name: Liposome-encapsulated Daunorubicin-Cytarabine

Description: Given IV

Arm Group Label: Arm I (CPX-351)

Intervention Type: Drug

Intervention Name: Cladribine

Description: Given IV

Arm Group Label: Arm II (CLAG-M)

Intervention Type: Drug

Intervention Name: Cytarabine

Description: Given IV

Arm Group Label: Arm II (CLAG-M)

Intervention Type: Biological

Intervention Name: Recombinant Granulocyte Colony-Stimulating Factor

Description: Given SC

Arm Group Label: Arm II (CLAG-M)

Intervention Type: Drug

Intervention Name: Mitoxantrone

Description: Given IV

Arm Group Label: Arm II (CLAG-M)

Intervention Type: Other

Intervention Name: Questionnaire Administration

Description: Ancillary studies

Intervention Type: Other

Intervention Name: Quality-of-Life Assessment

Description: Ancillary studies

Other Name: Quality of Life Assessment

Eligibility

Criteria:

Inclusion Criteria: - Diagnosis of untreated "high-grade" myeloid neoplasm (>=10% blasts in blood or bone marrow) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification. Outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered. Diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate - Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model - The use of hydroxyurea before enrollment is permitted; hydroxyurea should be discontinued prior to start of study treatment. Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL or with concern for other complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2) any time prior to enrollment - Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow) - Bilirubin < 2.0 mg/mL unless elevation is thought to be due to hepatic infiltration by neoplastic cells, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0) - Left ventricular ejection fraction (LVEF) >= 45%, assessed within 12 months prior to registration, e.g. by multigated acquisition scan (MUGA) scan or echocardiography or another appropriate diagnostic modality - Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable. Patients with fever thought to be likely secondary to leukemia are eligible - Known hypersensitivity to any study drug used in this trial - Pregnancy or active breast feeding - Concurrent treatment with any other approved or investigational anti-leukemia agent. Treatment with a FLT3-inhibitor for FLT3-mutated AML is permissible

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Roland Walter Principal Investigator Fred Hutch/University of Washington Cancer Consortium
Overall Contact

Last Name: Roland Walter

Phone: 206-667-3599

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Fred Hutch/University of Washington Cancer Consortium Roland Walter 206-667-3599 [email protected] Roland Walter Principal Investigator
Location Countries

United States

Verification Date

2021-03-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm I (CPX-351)

Type: Experimental

Description: INDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.

Label: Arm II (CLAG-M)

Type: Experimental

Description: INDUCTION: Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive an intermediate dose of cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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