A Study of TAK-659 in Combination With Bendamustine (+/-Rituximab), Gemcitabine, Lenalidomide, or Ibrutinib for the Treatment of Participants With Advanced Non-Hodgkin Lymphoma
The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of TAK-659 when administered in combination with bendamustine, bendamustine + rituximab, gemcitabine, lenalidomide, or ibrutinib.
A Phase 1b, Dose Escalation Study to Determine the Recommended Phase 2 Dose of TAK-659 in Combination With Bendamustine (±Rituximab), Gemcitabine, Lenalidomide, or Ibrutinib for the Treatment of Patients With Advanced Non-Hodgkin Lymphoma After At Least 1 Prior Line of Therapy
The drug being tested in this study is called TAK-659. TAK-659 is being tested to treat people who have advanced non-Hodgkin lymphoma. This study will determine the MTD or RP2D for TAK-659 in combination with bendamustine, bendamustine + rituximab, gemcitabine, lenalidomide, and ibrutinib. The study will enroll approximately 100 participants. Participants will be assigned to one of the 5 treatment groups:
- TAK-659 + Bendamustine
- TAK-659 + Bendamustine + Rituximab
- TAK-659 + Gemcitabine
- TAK-659 + Lenalidomide
- TAK-659 + Ibrutinib
This multi-center trial will be conducted in North America and Europe. The overall time to participate in this study is approximately 27 months. Participants will make multiple visits to the clinic and will be followed up for safety for 28 days after the last dose of study drug.
Lymphoma, Non-Hodgkin Drug Therapy Lymphoma Gemcitabine Thalidomide Lenalidomide Rituximab Bendamustine Hydrochloride TAK-659 Bendamustine Ibrutinib
You can join if…
Open to people ages 18 years and up
- Male or female participants aged 18 years or older.
- Histologically or cytologically confirmed diagnosis of advanced non-Hodgkin lymphoma(NHL) of any histology (with the exception of participants with Waldenström macroglobulinemia [WM] and chronic lymphocytic leukemia [CLL]).
- Radiographically or clinically measurable disease with at least 1 target lesion per International Working Group (IWG) criteria for malignant lymphoma.
- Participants who are refractory or relapsed after at least 1 prior line of therapy and for whom no effective standard therapy is available per the investigator's assessment.
- Either treatment naive to, relapsed/refractory to, or experienced treatment failure due to other reasons with ibrutinib, idelalisib, or any other investigational B-cell receptor (BCR) pathway inhibitors not directly targeting spleen tyrosine kinase (SYK).
- Prior treatment with a regimen that includes the combination drug will not necessarily exclude a participant from that cohort if the investigator views treatment with that agent as appropriate. However, a participant who has a contraindication for a particular combination agent or who has been discontinued from prior therapy with a particular agent for toxicity will not be eligible for inclusion in that particular cohort.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and life expectancy of greater than 3 months.
- Participants must have adequate organ function, including the following:
- Adequate bone marrow reserve: absolute neutrophil count (ANC) greater than or equal to (>=) 1000 per micro litre (/mcL), platelet count >=75,000/mcL(>=50,000/mcL for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL) (red blood cell [RBC] and platelet transfusion allowed>=14 days before assessment).
Hepatic: total bilirubin less than or equal to (<=) 1.5the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and AST <=2.5ULN.
- Renal: serum creatinine >=60 milliliter per minute (mL/min) either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours).
- Lipase ≤1.5×ULN and amylase ≤1.5×ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis.
- Blood pressure ≤Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to ≤ Grade 1 by hypertensive medications and glycosylated hemoglobin is ≤6.5%).
- Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, or
- Are surgically sterile, or
- If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar,ovulation, symptothermal, postovulation methods] withdrawal, spermicides only,and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
Male participant, even if surgically sterilized (that is, status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar,ovulation, symptothermal, postovulation methods], withdrawal, spermicides only,and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
- Both men and women in the rituximab combination arm (Cohort B) must practice contraception as described above from the time of signing of the informed consent form(ICF) through 12 months after the last dose of study drug.
- Both men and women in the lenalidomide combination arm (Cohort D) must adhere to the guidelines of the RevAssist program (United States participants) or, if not using commercial supplies, must adhere to the Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual.
- . Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
- . Recovered (that is, <= Grade 1 toxicity) from the reversible effects of prior anticancer therapy.
You CAN'T join if...
- Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or computed tomography (CT)scan/magnetic resonance imaging (MRI). Exceptions include those participants who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and do not have neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs).
- Known human immunodeficiency virus (HIV)-related malignancy.
- Known hypersensitivity (example, anaphylactic and anaphylactoid reactions) to any particular combination drug will result in a participant being ineligible for inclusion in that particular cohort.
- For participant in the lenalidomide combination arm, demonstrated hypersensitivity(example, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide.
- History of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field(fibrosis) is permitted.
- Life-threatening illness unrelated to cancer that could, in the investigator's opinion, make the participant not appropriate for this study.
- Female participants who are lactating and breast-feeding or a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.
- Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Known HIV positive.
- . Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
- . Systemic anticancer treatment (including investigational agents) or radiotherapy less than 2 weeks before the first dose of study treatment (<=4 weeks for large molecule agents).
- . Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1 or allogeneic stem cell transplant any time.
- . Any clinically significant comorbidities, such as uncontrolled pulmonary disease,known impaired cardiac function or clinically significant cardiac disease (specified below), active CNS disease, active infection, or any other condition that could compromise the participant's participation in the study.
- . Participants with any of the following cardiovascular conditions are excluded:
- Acute myocardial infarction within 6 months before starting study drug.
- Current or history of New York Heart Association Class III or IV heart failure.
- Evidence of current, uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Friderichia corrected QT interval (QTcF) >450 milliseconds (msec) (men) or >475 msec (women) on a 12-lead electrocardiogram (ECG) during the Screening period.
- Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that, in the opinion of the investigator, are considered to be clinically significant.
- . Lack of suitable venous access for the study-required blood sampling for TAK-659.
- . For participants in all combination arms (Cohorts A-E), use or consumption of any of the following substances:
- Medications or supplements that are known to be inhibitors of P-glycoprotein(P-gp) and/or strong reversible inhibitors of cytochrome P450 (CYP) 3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known) or within 7 days (if a reasonable half-life estimate is unknown) before the first dose of study drug. In general, the use of these agents is not permitted during the study except in cases in which an AE must be managed. See a nonexhaustive list of prohibited strong CYP3A reversible inhibitors and/or P-gp inhibitors based on the US Food and Drug Administration (FDA) Draft Drug-Drug Interactions(DDI) Guidance.
- Medications or supplements that are known to be strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days or within 5 times the inhibitor or inducer half-life (whichever is longer) before the first dose of study drug. The use of these agents is not permitted during the study.See a list of prohibited strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers based on the US FDA Draft DDI Guidance.
- Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study.
- . Additionally, for participants in the ibrutinib combination arm (Cohort E), use or consumption of any of the following substances:
- Medications or supplements that are known to be moderate reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known) or within 7 days (if a reasonable half-life estimate is unknown) before the first dose of study drugs. In general, the use of these agents is not permitted during the study for this combination except in cases in which an AE must be managed. See a list of nonexhaustive moderate CYP3A reversible inhibitors based on the US FDA Draft DDI Guidance.
- Medications or supplements that are known to be moderate mechanism-based inhibitors or moderate inducers of CYP3A within 7 days or within 5 times the inhibitor or inducer half-life (whichever is longer) before the first dose of study drugs. In general, the use of these agents is not permitted during the study for this combination except in cases in which an AE must be managed. See a list of nonexhaustive moderate CYP3A mechanism-based inhibitors or moderate CYP3A inducers based on the US FDA Draft DDI Guidance.
- Seville oranges within 5 days before the first dose of study drugs and during the study.
- . Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
- . Systemic infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
- . Participants with another malignancy within 2 years of study start. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry.
- . Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659 including difficulty swallowing tablets or diarrhea>Grade 1 despite supportive therapy.
- . Treatment with high-dose corticosteroids for anticancer purposes within 14 days before the first dose of TAK-659; daily dose equivalent to 10 mg oral prednisone or less is permitted. Corticosteroids for topical use or in nasal spray or inhalers are allowed.
- University of California San Diego (UCSD) - Moores Cancer Center accepting new patients
La Jolla, California, 92093, United States
- Cedars-Sinai Medical Center (CSMC) - Samuel Oschin Comprehensive Cancer Institute not yet accepting patients
West Hollywood, California, 90048, United States
- accepting new patients
- Start Date
- Completion Date
- Millennium Pharmaceuticals, Inc.
- Phase 1
- Study Type
- Last Updated
- March 9, 2018
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