Study of Combination Ruxolitinib and Decitabine Treatment for Accelerated Phase MPN or Post-MPN AML

NCT02076191 | Completed Phase 1 DMC

• 3 other identifiers: GCO 13-1816MPD-RC 109P01CA108671
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to test the safety and tolerability of ruxolitinib at different dose levels in combination with decitabine and the effectiveness of ruxolitinib in combination with decitabine in patients with accelerated or blast phase Myeloproliferative Neoplasm (MPN), which is a group of diseases of the bone marrow in which excess cells are produced. Ruxolitinib is a drug that is approved by the Federal Drug Administration (FDA) for the treatment of patients with advanced forms of myelofibrosis. It inhibits the Jak proteins that are often abnormal in MPN. A recent clinical study showed that ruxolitinib treatment could put some patients with this disease into remission. Decitabine is a chemotherapy, approved by the Federal Drug Administration (FDA), that has been used to treat acute leukemia. It works in some patients, but most patients with accelerated and blastic MPN do not respond to treatment. Ruxolitinib and decitabine will be combined in this study to find out what dose of the two medicines are safe together. Using Ruxolitinib in combination with Decitabine is experimental. The investigators want to find out what effects, good and/or bad it has on the patient and the disease.

Conditions

Myeloproliferative Neoplasms

Keywords

Ruxolitinib; Decitabine; Myeloproliferative Neoplasms; Combination Therapy

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Safety and efficacy of ruxolitinib when used in combination with decitabine. MTD is defined as the highest dose studied for which the incidence of (Dose Limiting Toxicities) DLT is at least 33%.

  up to 5 weeks

• Dose Limiting Toxicities (DLT)

  Safety and efficacy of ruxolitinib when used in combination with decitabine. DLTs will be defined as those adverse events occurring in the first 5 weeks after initiation of therapy that are not clearly related to disease.

  up to 5 weeks

Secondary Outcomes (1)

• Recommended Phase II Dose (RPTD)

  up to 20 weeks

Study Arms (1)

Myeloproliferative neoplasms

EXPERIMENTAL

In phase I, increasing doses of ruxolitinib in combination with decitabine at a dose of 20 mg/m2 daily intravenously over 5 days. An initial dose of ruxolitinib of 10 mg orally twice daily is anticipated with planned, dose escalations of 15 mg orally twice daily, 25 mg orally twice daily and 50 mg orally twice daily. The dose can also be de-escalated to 5mg orally twice daily if dose limiting toxicities (DLTs) are observed at the initial 10mg dose. Patients will receive ruxolitinib as a single agent for the first 7 days followed by the administration of decitabine on day 8 for a total of 5 consecutive days. Patients will continue ruxolitinib at the assigned dose through the first cycle and may reduce the dose for specified toxicity beginning with the second cycle. Patients in Phase II will start at the recommended phase II dose (RPTD) of ruxolitinib in combination with decitabine at a dose of 20 mg/m2 daily intravenously over 5 days.

Drug: Ruxolitinib; Drug: Decitabine

Interventions

Ruxolitinib DRUG

Ruxolitinib will be administered at doses of 5mg, 10mg, 15mg, or 25 mg taken orally every 12 hours throughout the treatment cycle.

Myeloproliferative neoplasms

Decitabine DRUG

Decitabine is administered intravenously at a dose of 20 mg/m2 daily for 5 days. Subsequent cycles of decitabine may be administered at 4 week intervals as clinically tolerated. Decitabine treatment may be deferred for up to 2 weeks to allow recovery from non-hematologic toxicity during the first 6 cycles and up to 2 weeks thereafter for hematologic toxicities as well. The first treatment cycle will last 35 days and will be the evaluable period for DLTs and RPTD determination for patients enrolled in the phase I portion only. Subsequent treatment cycles will be 4-6 weeks in duration as defined by decitabine administration.

Myeloproliferative neoplasms

Eligibility Criteria

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

You may qualify if:

• Accelerated phase MPN as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of acute myelogenous leukemia as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF.
• \>18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to accelerated or blastic phase MPN and not due to another comorbidity.
• Acceptable pre-study organ function during screening as defined as: Total bilirubin \< 1.5 times the upper limit of normal (ULN) unless due to Gilbert's disease or hemolysis, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN, Serum creatinine ≤ 1.5 x ULN
• Women of childbearing potential and males must agree to use adequate contraception (i.e., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately.
• Patients who are not candidates for or have declined an allograft.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Patients with acute myelofibrosis are excluded.
• Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Other medications, severe acute/chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, that in the judgment of the Investigator would make the subject inappropriate for entry into this study.

Sponsors & Collaborators

• John Mascarenhas: lead
• Myeloproliferative Disorders-Research Consortium: collaborator
• National Cancer Institute (NCI): collaborator
• Incyte Corporation: collaborator

Study Sites (8)

Washington University of St. Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Taussig Cancer Center Institute

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Mascarenhas JO, Rampal RK, Kosiorek HE, Bhave R, Hexner E, Wang ES, Gerds A, Abboud CN, Kremyanskaya M, Berenzon D, Odenike O, Farnoud N, Krishnan A, Weinberg RS, McGovern E, Salama ME, Najfeld V, Medina-Martinez JS, Arango Ossa JE, Levine MF, Zhou Y, Sandy L, Heaney ML, Levine RL, Mesa RA, Dueck AC, Hoffman R. Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase. Blood Adv. 2020 Oct 27;4(20):5246-5256. doi: 10.1182/bloodadvances.2020002119.

  PMID: 33104796 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

ruxolitinib; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Ronald Hoffman, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: February 1, 2014
• Primary Completion: July 20, 2018
• Study Completion: July 20, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Locations

US (8)