Phase I Trial of the Combination of Ibrutinib and Lenalidomide for the Treatment of Patients With MDS Who Have Failed or Refuse Standard Therapy
Overview
- Phase
- Phase 1
- Intervention
- Ibrutinib
- Conditions
- Myelodysplastic Syndrome
- Sponsor
- University of California, Davis
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
This phase I trial studies the side effects and best dose of ibrutinib when giving together with lenalidomide in treating patients with myelodysplastic syndrome. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, 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. Giving ibrutinib and lenalidomide may work better in treating patients with myelodysplastic syndrome.
Detailed Description
PRIMARY OBJECTIVES: To determine the recommended Phase II dose (RP2D) for ibrutinib in combination with lenalidomide in patients with myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: To do an early assessment of the activity of the combination of ibrutinib and lenalidomide in patients with MDS. TERTIARY OBJECTIVES: To examine the pharmacodynamic and biological effects of the combination of ibrutinib and lenalidomide in MDS.
Investigators
Brian Jonas
Principal Investigator
University of California, Davis
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed diagnosis of MDS by World Health Organization (WHO) criteria (including secondary and therapy-related disease) who have failed standard therapy, who are intolerant of prior therapy, or who refuse standard therapy; any prior therapy, including ibrutinib and/or lenalidomide (unless intolerant of one or both of these medications), is permitted
- •Hypomethylating agent failure is defined as disease progression or stable disease as best response to an adequate course of treatment (at least four cycles) with an injectable hypomethylating agent (azacitidine or decitabine)
- •International Prognostic Scoring System (IPSS)-revised (R) intermediate, high or very high risk disease
- •No specific hematologic parameters for study entry are required; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm\^3
- •Serum aspartate transaminase (AST) or alanine transaminase (ALT) less than or equal to 3.0 x upper limit of normal (ULN)
- •Estimated creatinine clearance greater than or equal to 60 ml/min (Cockcroft-Gault)
- •Bilirubin less than or equal to 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- •Prothrombin time (PT)/international normalized ratio (INR) less than or equal to 1.5 x ULN and partial thromboplastin time (PTT) (activated \[a\]PTT) less than or equal to 1.5 x ULN
- •Karnofsky performance status (KPS) performance status of 60% or greater
- •Ability to understand and willingness to sign an informed consent form
Exclusion Criteria
- •Anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug; hydroxyurea is permitted up to the day before initiation of study treatment
- •Prior allogeneic (allo)-hematopoietic cell transplantation (HCT) less than three months from the time of enrollment
- •Acute graft versus host disease (GVHD) or active chronic GVHD greater than grade 1
- •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration \[\> 14 days\] of \> 60 mg/day of prednisone or equivalent) within 28 days of the first dose of study drug
- •History of allergy to or intolerance of ibrutinib or lenalidomide
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- •Recent culture-documented infection requiring systemic intravenous treatment that was completed =\< 7 days before the first dose of study drug or any uncontrolled active systemic infection; fever of unknown origin is not an exclusion criterion, as this may be disease-related
- •Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade 2 or less, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
- •Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- •History of stroke or intracranial hemorrhage within 3 months prior to enrollment
Arms & Interventions
Treatment (lenalidomide, ibrutinib)
Patients receive lenalidomide PO QD on days 1-21 and ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Intervention: Ibrutinib
Treatment (lenalidomide, ibrutinib)
Patients receive lenalidomide PO QD on days 1-21 and ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Maximum tolerated dose
Time Frame: Up to 28 days
Data will be reported in tables with descriptive statistics used. Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Effects (CTCAE) version 4.03. Tables will be created to summarize the toxicities and adverse effects by dose, course, organ and severity as well as the study demographics.
Secondary Outcomes
- Overall survival(From the time of first study drug administration until the date of death from any cause, assessed up to 6 months)
- Disease free survival(From the time of first documented complete response until relapse or the date of death from any cause, assessed up to 6 months)
- Hematologic normalization rate(Up to 6 months)
- Disease response(Up to 6 months)
- Progression free survival(From the time of first study drug administration until the date of progression or death from any cause, assessed up to 6 months)
- Time to response(From the time of first study drug administration to the date of complete remission, partial remission, or hematologic improvement, assessed up to 6 months)