Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

NCT01895842 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2013-0012NCI-2013-02204
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with low or intermediate-1 risk MDS. The safety of this drug will also be studied, and whether it can help to control the disease.

Conditions

Leukemia

Keywords

Leukemia; Myelodysplastic syndrome; MDS; Low or intermediate-1 risk; Maximum tolerated dose; MTD; Ruxolitinib; Jakafi; INCB018424; INC424

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Ruxolitinib

  Maximum tolerated dose (MTD) is the maximum dose at which \<33% of patients experience a dose limiting toxicity (DLT). Dose limiting toxicity defined as any grade 3 or higher non-hematologic toxicity.

  28 days

Secondary Outcomes (1)

• Number of Participants with Response of Ruxolitinib

  8 weeks

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

Part 1: Dose of ruxolitinib received will depend when patient joined study. The first group of patients receive the lowest dose of ruxolitinib. Starting dose level for Part 1, 5 mg by mouth twice a day for a 28 day cycle. The second group of patients receive the lowest dose of ruxolitinib for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. The third group of patients receive the higher dose taken by the second group for 1 cycle and if no intolerable side effects are seen, the dose will be increased for Cycles 2 and beyond. The fourth group of patients take the higher dose taken by the third group for 1 cycle and if no intolerable side effects are seen, the dose will increase to the next higher dose for Cycles 2 and beyond. If patients enrolled in Part 2, they will receive ruxolitinib at the highest dose that was tolerated in Part 1.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Starting dose level for Part 1: 5 mg by mouth twice a day for a 28 day cycle. Starting dose level for Part 2: Maximum tolerated dose from Part 1.

Also known as: Jakafi, INCB018424, INC424

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Patients with previously treated low or intermediate-1 risk MDS by the IPSS classification (this is defined in table 1)
• Patients must have one of the following: elevated b2-microglobulin levels (defined as 2 times compared to normal), carry a JAK2 mutation, or presence of phosphorylated p65 NF-kB component in at least 5% of bone marrow cells.
• Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
• Age \>/= 18 years old
• Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or other investigational agents are allowed. A four week wash out period will be required before receiving study medication.
• Patients must have the following non-hematologic values Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \</= 2.5 x Upper Limit of Normal (ULN) or \</= 5.0 x ULN if hepatic involvement is present; Serum bilirubin \</= 2 x ULN; Serum creatinine \</= 2 x ULN or 24-hour creatinine clearance \>/= 60 ml/min
• Patients with Childbearing potential must agree to use appropriate forms of birth control

You may not qualify if:

• Previously untreated low or intermediate-1 risk MDS patients because there are approved therapies for these patients.
• Uncontrolled undercurrent illness that in the opinion of the treating physician would contraindicate the use of the drug.
• Patients with active infections including uncontrolled HIV infection, active hepatitis B, C, or any other symptomatic systemic infection requiring active therapy will be excluded from study
• Patients receiving potent CYP3A4 (such as but not limited to boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) inhibitors will be excluded from the study.
• Women who are pregnant or lactating.
• Patients with a white blood cell count of more than 30x10\^3 K/uL will not be eligible for this study.
• Patients that have received prior allogeneic stem cell transplantation are excluded from this study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Abaza Y, Hidalgo-Lopez JE, Verstovsek S, Jabbour E, Ravandi F, Borthakur G, Estrov Z, Alvarado Y, Burger J, Schneider H, Soltysiak KA, Wei Y, Kantarjian HM, Bueso-Ramos CE, Garcia-Manero G. Phase I study of ruxolitinib in previously treated patients with low or intermediate-1 risk myelodysplastic syndrome with evidence of NF-kB activation. Leuk Res. 2018 Oct;73:78-85. doi: 10.1016/j.leukres.2018.09.004. Epub 2018 Sep 14.

  PMID: 30245189 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  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

Study Record Dates

• First Submitted: July 5, 2013
• First Posted: July 11, 2013
• Study Start: February 1, 2014
• Primary Completion: April 2, 2019
• Study Completion: April 2, 2019
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

US (1)