A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib

NCT01776723 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCC-17259
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug \[ruxolitinib\] can improve outcomes of patients with CMML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). It has already been studied in a number of patients with different bone marrow diseases and is approved for the treatment of a disease called Myelofibrosis; however, it is not approved for treatment of CMML. It is given orally (by mouth). Most people tolerate it well but the tolerability has not been determined in patients with CMML. We will be testing different doses to determine how much of the medication people can tolerate (bear) before they develop side effects.

Conditions

Myelomonocytic Leukemia

Keywords

Chronic Myelomonocytic Leukemia; CMML; Leukemia

Outcome Measures

Primary Outcomes (2)

• The Maximum Tolerated Dose (MTD) of Ruxolitinib for the Treatment of Myelomonocytic Leukemia (CMML)

  Phase I - The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT). Dose-limiting toxicity (DLT) is defined as any grade 4 hematologic toxicity and any grade 3 or greater non-hematologic toxicity except nausea that is controlled by antiemetic therapy based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3 metabolic/electrolyte abnormalities that are not clinically significant, and are adequately controlled within 72 hours are not to be considered a DLT.

  17 weeks

• Occurrence of Clinical Response

  Phase II - Proportion of participants achieving clinical benefit defined as hematologic improvement, complete remission (CR), partial remission (PR), marrow complete remission (Marrow CR) or stable disease (SD) by the International Working Group (IWG) 2006 criteria. Erythroid Response for pretreatment hemoglobin \< 11 g/dl; Platelet response for subjects with a pre-treatment platelet count \< 50 x 10\^9/L; Neutrophil response with pretreatment absolute neutrophil count (ANC) \< 1 x 10\^9/L.

  Up to 2 years

Secondary Outcomes (3)

• Percentage of Participants With Acute Myeloid Leukemia (AML) Transformation

  Up to 2 years

• Median Overall Survival (OS)

  Up to 2 years

• Duration of Response in Days

  3.5 years

Study Arms (2)

I: Dose Escalation - Ruxolitinib

EXPERIMENTAL

Phase I: Dose Escalation. In Phase I, participants will be allocated to dose levels starting at 10 mg/d (twice a day \[BID\] dosing) according to the "rolling six" Phase I design.

Drug: Ruxolitinib

II: Maximum Tolerated Dose - Ruxolitinib

EXPERIMENTAL

Phase II: Treatment at Maximum Tolerated Dose (MTD).

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

In Phase I, participants will be allocated to twice a day (BID) doses of 10 mg/d up to 40mg/d. The starting dose will be 10 mg/d (5mg BID). Each cohort will include up to 6 subjects. Once MTD is reached, 10 additional participants will be treated during the first stage of Phase II (stage 1) at the MTD.

Also known as: Jakafi®, INCB-018424, Kinase Inhibitor

I: Dose Escalation - Ruxolitinib; II: Maximum Tolerated Dose - Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of CMML using the World Health Organization (WHO) classification
• Age \>18 years at the time of obtaining informed consent
• Must be able to adhere to the study visit schedule and other protocol requirements
• Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2
• Women of childbearing potential must have a negative pregnancy test at time of screening and baseline visits and agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
• Must understand and voluntarily sign an informed consent form
• Must have a life expectancy of greater than 3 months at time of screening

You may not qualify if:

• Platelet count of less than 35,000/uL
• Absolute Neutrophil Count (ANC) of less than 250/uL
• Serum Creatinine \>2.0
• Serum total bilirubin \>1.5 x upper limit of normal (ULN)
• Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment
• Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study
• Concurrent use of Granulocyte/macrophage colony stimulating factor (GM-CSF). Granulocyte colony-stimulating factor (G-CSF) could be used for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents that were started \>8 weeks from first ruxolitinib dose or corticosteroids that were being administered prior to screening are allowed.
• Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because ruxolitinib has not been studied in pregnant subjects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.
• Patients who have participated in other interventional (treatment-related) clinical trials within 30 days of enrollment are excluded.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Incyte Corporation: collaborator

Study Sites (6)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Weill Medical College of Cornell

New York, New York, 10021, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Leukemia

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Eric Padron, MD
• Organization: H Lee Moffitt Cancer Center & Research Institute

Eric.Padron@Moffitt.org

813-745-3907

Study Officials

• Eric Padron, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2013
• First Posted: January 28, 2013
• Study Start: February 20, 2013
• Primary Completion: November 28, 2018
• Study Completion: May 10, 2022
• Last Updated: September 22, 2022
• Results First Posted: March 12, 2020

Record last verified: 2022-09

Locations

US (6)