Testing the Effect of Taking Ruxolitinib and CPX-351 in Combination for the Treatment of Advanced Phase Myeloproliferative Neoplasms

NCT03878199 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: OSU-20393NCI-2019-03712
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II trial studies the best dose of ruxolitinib when given together with CPX-351 and to see how well they work in treating patients with accelerated phase or blast phase myeloproliferative neoplasm. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. CPX-351 is a mixture of 2 chemotherapy drugs (daunorubicin and cytarabine) given for leukemia in small fat-based particles (liposomes) to improve the drug getting into cancer cells. Giving ruxolitinib and CPX-351 may work better in treating patients with secondary acute myeloid leukemia compared to CPX-351 alone.

Conditions

Polycythemia Vera; Secondary Acute Myeloid Leukemia; Essential Thrombocythemia; Myelofibrosis; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) (Phase I)

  DLT occurrence after exposure to ruxolitinib and CPX-351.

  Day 1 to day 42

• Proportion of Participants That Achieve at Least an Acute Leukemia Response-Partial Response (>= ALR-P, Per 2012 Myeloproliferative Neoplasm - Blast Phase [MPN-BP] Criteria) (Phase 2)

  Will compute the proportion of efficacy-evaluable participants achieving objective response rate (ORR) and the exact binominal 95% confidence interval. The ORR will be calculated as the proportion of participants that achieve at least an Acute Leukemia Response-Partial response (≥ ALR-P, per 2012 MPN-BP criteria).

  Day 1 to end of induction or re-induction cycle (or upon assessment of the bone marrow biopsy performed near the end of these cycles if this occurs later). Cycle length is 28 days.

Secondary Outcomes (6)

• Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  Up to 30 days after last on-study dose, up to 9 months.

• Overall Survival (OS)

  Up to 4 years.

• Event-free Survival (EFS)

  Day 1 to treatment failure, progressive disease, relapse, last exam date, or death (whichever is first), up to 2 years

• Relapse-free Survival (RFS)

  Date of first documented response (ALR-C) to date of relapse or death from any cause, up to 2 years.

• Remission Duration

  Date of first documented response (ALR-C) to date of documented relapse, up to 2 years

Other Outcomes (6)

• Proportion of Participants That Achieve at Least a Complete Remission With Incomplete Marrow Recovery (CRi) (Per European Leukemia Net [ELN] Criteria)

  Day 1 to end of induction or re-induction cycle (up to 8 weeks after start of study treatment)

• Rate of CCR; Which is the Proportion of Participants That Achieve at Least a MLFS (Per ELN Criteria)

  Day 1 to end of induction or re-induction cycle (up to 8 weeks after start of study treatment)

• Proportion of Participants Who Have an Minimal Residual Disease (MRD) Negative Status

  End of induction, up to 2 months on study

Study Arms (1)

Treatment (CPX-351, ruxolitinib, allogeneic SCT)

EXPERIMENTAL

See Detailed Description.

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic SCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (CPX-351, ruxolitinib, allogeneic SCT)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

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

Treatment (CPX-351, ruxolitinib, allogeneic SCT)

Ruxolitinib DRUG

Given PO

Also known as: INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424

Treatment (CPX-351, ruxolitinib, allogeneic SCT)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Participants eligible for this study have either MPN in accelerated phase (AP) or blast phase (BP), defined as:
• MPN-AP is defined by 10% to 19% blasts in the peripheral blood or bone marrow
• MPN-BP is defined by \>= 20% blasts in the blood or bone marrow
• Either MPN-AP or MPN-BP requires a previous diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), primary or secondary myelofibrosis (MF), or MDS/MPN overlap with intermediate-2 or high risk disease according to IPSS as well as progression on or failure to respond to at least one line of therapy
• Participants with ET, PV, or MF that have received prior MPN-associated therapy (e.g., hydroxyurea, hypomethylating agents \[azacitidine, decitabine\], anti-platelet therapies \[e.g., aspirin, anagrelide\], as well as JAK2 inhibitor therapy \[e.g., ruxolitinib or other investigational JAK2 inhibitor\]) are eligible. They must discontinue prior to starting therapy; no wash-out is required
• Female participants of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 30 days following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Male participants of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days until the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment
• Left ventricular ejection fraction at \>= 50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan (14 days prior to initiating study treatment)
• Candidate for cytotoxic-intensive induction chemotherapy
• Willing to take oral medication
• Serum creatinine =\< 2 x the upper limit of normal (ULN), or glomerular filtration rate \> 20 ml/min/1.73m\^2 as calculated by Cockcroft-Gault formula
• Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits or can be corrected with supplementation
• Total serum bilirubin =\< 2.5 x ULN

You may not qualify if:

• Ongoing participation in another clinical trial
• Isolated myeloid sarcoma (i.e., participants must have blood or marrow involvement with AML to enter the study)
• Acute promyelocytic leukemia (French-American-British \[FAB\] M3 classification)
• Active central nervous system (CNS) involvement by AML
• Current treatment or treatment within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study medication with another investigational medication or current enrollment in another investigational drug protocol (unless there is evidence of rapidly progressive disease in which case a shorter interval from last therapy may be acceptable)
• Any unresolved toxicity equal to or greater than grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve, such as peripheral neurotoxicity
• Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry, excluding the placement of vascular access
• Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
• Participants with rapidly progressive disease (defined by blast count doubling within 48 hours) or organ dysfunction that would prevent them from receiving these agents
• Participants with uncontrolled infection will not be enrolled until infection is treated and symptoms controlled
• Participants with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for \>= 72 hours (hrs)
• Known hypersensitivity to ruxolitinib, cytarabine, daunorubicin, or liposomal products
• History of Wilson's disease or other copper metabolism disorder
• Uncontrolled intercurrent illness or any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol per investigator's discretion. Including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias
• Participants with prior cumulative anthracycline exposure of greater than 368 mg/m\^2 daunorubicin (or equivalent)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Incyte Corporation: collaborator
• Jazz Pharmaceuticals: collaborator

Study Sites (3)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

OHSU

Portland, Oregon, 97239, United States

Location

Simmons Cancer Center

Dallas, Texas, 75390, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Thrombocythemia, Essential; Primary Myelofibrosis; Myeloproliferative Disorders; Polycythemia Vera

Interventions

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

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Uma Borate
• Organization: Ohio State University Comprehensive Cancer Center

uma.borate@osumc.edu

614-685-9828

Study Officials

• Uma Borate, MD

  The Ohio State Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 18, 2019
• Study Start: February 20, 2019
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: April 24, 2026
• Results First Posted: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)