CPX-351 Plus Enasidenib for Relapsed AML

NCT03825796 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 18-001416NCI-2018-02998
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as CPX-351, 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. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 and enasidenib may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.

Conditions

Recurrent Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy

  Up to day 60

Secondary Outcomes (6)

• Proportion of patients with persistent grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  At day 60

• Proportion of patients who achieve CR/CRi during maintenance therapy

  Up to 2 years

• Proportion of patients who achieve CR/complete remission with partial hematologic recovery (CRp) after induction therapy

  Up to 2 years

• Time to return of normal hematopoiesis

  From day 1 of induction assessed up to 2 years

• Overall survival

  From day 1 of induction therapy, assessed at day 30 and 60

Other Outcomes (5)

• Proportion of patients who have a particular co-occurring mutation with an allelic frequency >= 10% along with the IDH2 mutation, and have achieved CR/CRi

  Up to 2 years

• Proportion of patients who achieved CR/CRi then achieve minimal residual disease negativity based on Invivoscribe assay

  Up to 2 years

• Proportion of abnormal troponin levels without concurrent elevated creatinine

  Up to 2 years

Study Arms (1)

Treatment (CPX-351, enasidenib mesylate)

EXPERIMENTAL

See detailed description

Drug: Enasidenib Mesylate; Drug: Liposome-encapsulated Daunorubicin-Cytarabine

Interventions

Enasidenib Mesylate DRUG

Given PO

Also known as: 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007, Enasidenib Methanesulfonate, Idhifa

Treatment (CPX-351, enasidenib mesylate)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

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

Treatment (CPX-351, enasidenib mesylate)

Eligibility Criteria

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

You may qualify if:

• Bone marrow blasts \>= 5% that develops after CR/CRi in patient with prior history of AML, no restriction on prior number of relapses or regimens
• AML characterized by the IDH2 gene mutation, without requirement for a particular allelic frequency
• Patients previously treated with IDH2 inhibitor can be enrolled
• At least a 3-month duration of CR/CRi prior to relapse
• Relapses after allogeneic HSCT are included with a minimum of 3 from the date of allogeneic HSCT
• Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Serum total bilirubin \< 2.0 mg/dL, unless considered due to Gilbert's disease or leukemic involvement
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 times the upper limit of normal, unless considered due to leukemic involvement
• Alkaline phosphatase \< 3 times the upper limit of normal, unless considered due to leukemic involvement
• Serum creatinine =\< 2.0 mg/dL, or creatinine clearance \> 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
• Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for four months (females and males) following the last dose of IDH inhibitor. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (eg, synthetic condoms, diaphragm or cervical cap with spermicidal foam, cream, or gel) or male partner sterilization

You may not qualify if:

• Concurrent FLT3 mutation that the treating physician deems necessary to treat with FLT3-targeted therapy; whereas, patients with FLT3-mutated AML not treated with FLT3-targeted therapy can be enrolled
• Acute promyelocytic leukemia
• Inability to swallow medications or history of gastrointestinal (GI) malabsorptive disease
• Active malignancy that would limit survival by less than two years
• New York Heart Association class III or VI
• Left ventricular ejection fraction \< 40%
• History of coronary stent placement that require mandatory continuation of dual-antiplatelet therapy
• Baseline QT corrected interval based on Fridericia's formula (QTcF) interval \> 450 ms
• History of Wilson's disease or other copper handling disorders
• Hypersensitivity to cytarabine, daunorubicin, or liposomal products
• Active invasive fungal infection
• Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
• Lifetime cumulative daunorubicin-equivalent anthracycline dose \> 368 mg/m\^2
• Pregnant or breast feeding

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (3)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

2-Propanol; methanesulfonic acid; enasidenib; CPX-351; Injections; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Propanols; Alcohols; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Caspian Oliai, MD

  UCLA / Jonsson Comprehensive Cancer Center

  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: January 30, 2019
• First Posted: January 31, 2019
• Study Start: April 12, 2019
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

US (3)