Advanced Solid Tumor and Lymphoma MalignanciesPhase 1NCT02000934
A Study of TAK-659 in Adult Participants With Advanced Solid Tumor and Lymphoma Malignancies
A Phase 1 study testing TAK-659 in people with Advanced Solid Tumor and Lymphoma Malignancies, run by Calithera Biosciences, Inc at 15 sites in 4 countries.
Trial summary
This study is an open-label, multicenter, phase 1, dose escalation study of TAK-659 in adult participants with advanced solid tumor and lymphoma malignancies. This study will be the first to administer TAK-659 to humans. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor and Lymphoma Malignancies
- What is being tested?
- TAK-659
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 15 sitesin 4 countries
- Study dates
- 31 Dec 2013to 29 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each participant must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female participants 18 years or older.
- To be enrolled to the dose escalation (Part A), participants must have
- histologically or cytologically confirmed diagnosis of metastatic and/or advanced solid tumor malignancy or lymphoma, for which no effective standard treatment is available. However, participants with primary brain tumors or WM will be excluded.
- Radiographically or clinically measurable or nonmeasurable (but evaluable) disease. Radiographically measurable disease is determined by RECIST (version 1.1) for solid tumors or by International Working Group (IWG) criteria for malignant lymphoma (2007 IWG).
- To be enrolled to the dose expansion cohorts (Part B), participants must meet the following criteria:
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- Diagnosis of CLL that meets International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for Cohort 1; pathologically confirmed diagnosis of DLBCL for Cohort 2; histologically confirmed diagnosis of B-cell NHL (follicular lymphoma [FL] [Grade 1, 2, or 3a], small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), marginal zone lymphoma (MZL) [splenic, nodal, or extra-nodal]) for Cohort 3; histologically confirmed diagnosis of MCL for Cohort 4; and histologically confirmed diagnosis of PTLD (early lesion, polymorphic, monomorphic, classical Hodgkin lymphoma-type, Epstein-Barr virus (EBV) -positive DLBCL of the elderly, DLBCL associated with chronic inflammation; along with documented or documentable Epstein-Barr virus-encoded small RNA (EBER) status by tissue in situ hybridization [ISH]) for Cohort 5; histologically confirmed DLBCL (de novo or transformed disease from iNHL) for Cohort 6.
- Must have received greater than or equal to (>=) 1 prior therapy (excluding radiation); documented PD (MCL); either treatment naïve to, relapsed/refractory to, or treatment failure due to other reasons with ibrutinib, idelalisib, or any other investigational B-cell receptor (BCR) in pathway inhibitors not directly targeting Spleen tyrosine kinase (SYK); considered not appropriate for treatment or retreatment with purine analog-based therapy (CLL); or considered ineligible for at least 1 prior therapy (PTLD); or relapsed or refractory to >= 2 prior lines of chemotherapy (including standard first line therapy including Rituximab and an anthracycline [or equivalent if contraindicated] and one additional systemic multiagent chemotherapy as second-line salvage therapy that may have included autologous stem cell transplant (ASCT) [unless ineligible for salvage therapy and ASCT]) and should not have failed more than 4 prior lines of therapy (DLBCL Cohort 6).
- Radiographically or clinically measurable and/or evaluable disease as specified in the protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Participants must have adequate organ function, including bone marrow reserve, hepatic, renal, pancreatic function and controlled blood pressure as described in the protocol.
- Female participants who are postmenopausal for at least 1 year, are surgically sterile, or if of childbearing potential who agree to use 2 effective method(s) of contraception during the study treatment period through 6 months after the last dose of study drug or practice true abstinence.
- Male participants, even if surgically sterilized, who agree to practice effective barrier contraception during the study treatment period through 6 months after the last dose of study drug or practice true abstinence.
- 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.
- Participants must have recovered from the reversible effects of prior anticancer therapy (to Grade less than or equal to (<=) 1).
Who cannot join
- Participants meeting any of the following exclusion criteria are not to be enrolled in the study.
- Participants with brain metastasis, or participants with central nervous system (CNS) lymphoma or participants with another malignancy within two years of study start, with exceptions as described in the protocol.
- 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.
- Life-threatening illness unrelated to cancer; major surgery within 14 days before the first dose of study drug; systemic infection requiring intravenous (IV) antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
- Female participants who are pregnant or lactating.
- Any immunotherapy, chemotherapy, radiotherapy, or investigational therapy within 3-4 weeks before the first dose of study treatment, as detailed in the protocol.
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- For escalation cohort or expansion cohorts excluding PTLD, ASCT within 6 months before Day 1 of Cycle 1, or prior ASCT at any time without full hematopoietic recovery before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.
- Treatment with high dose corticosteroids (> daily dose equivalent to 10 milligram (mg) oral prednisone) for anticancer purposes within 7 days before the first dose of TAK-659.
- Known human immunodeficiency virus (HIV) positive; known hepatitis B surface antigen-positive; or known or suspected active hepatitis C infection (testing not required).
- Evidence of currently uncontrolled cardiovascular conditions as listed in the protocol.
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659 including difficulty swallowing tablets; diarrhea > Grade 1 despite supportive therapy.
- Lack of suitable venous access for required blood sampling.
- Use or consumption of P-glycoprotein (P-gp) inducers/inhibitors and/or strong CYP3A inducers/inhibitors as described in the protocol, and grapefruit-containing food or beverages as described in the protocol.
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
United States5 sites
Northwestern University
Chicago, Illinois, 60611
The Methodist Hospital Research Institute
Houston, Texas, 77030
SCRI
Nashville, Tennessee, 37203
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900
Florida Cancer Specialists, Sarasota FL
Sarasota, Florida, 34232
Italy4 sites
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna, 40138
Ospedale San Raffaele U.O. di Ematologia e Trapianto di midollo osseo
Milan, 20132
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma, 00133
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Avda. Reyes Catolicos, 2
Madrid, 28040
Centro Integral Oncologico Clara Campal
Madrid, 28050
United Kingdom3 sites
University College London Hospitals
London, Greater London, WC1E 6AG
The Christie
Manchester, Greater Manchester, M20 4BX
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT
About this study
Official title: An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-659 in Adult Patients With Advanced Solid Tumor and Lymphoma Malignancies
This study is an open-label, multicenter, phase 1, dose escalation study of TAK-659 in adult participants with advanced solid tumor and lymphoma malignancies. This study will be the first to administer TAK-659 to humans. The participants population during dose escalation (Part A) will consist of adults previously diagnosed with any form of a solid tumor or lymphoma for which standard, curative, or life-prolonging treatment does not exist or is no longer effective. This first-in-human (FIH) study will include 5 dose expansion cohorts in refractory and/or relapsed Chronic Lymphocytic Leukemia (CLL), Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD) (Part B) following completion of dose escalation (Part A).
- Being tested
- TAK-659
- Keywords
- TAK-659, Solid Tumors, CLL, DLBCL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-659Drug
TAK-659 tablet
| Study group | Role | What they receive |
|---|---|---|
| TAK-659 60 mg (Dose Escalation) | Experimental | TAK-659 60 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 49 cycles). Receives: Drug: TAK-659 |
| TAK-659 80 mg (Dose Escalation) | Experimental | TAK-659 80 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 4 cycles). Receives: Drug: TAK-659 |
| TAK-659 100 mg (Dose Escalation) | Experimental | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 32 cycles). Receives: Drug: TAK-659 |
| TAK-659 120 mg (Dose Escalation) | Experimental | TAK-659 120 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 41 cycles). Receives: Drug: TAK-659 |
| TAK-659 CCL (Dose Expansion) | Experimental | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with chronic lymphocytic leukemia (CCL) (up to 6 cycles). Receives: Drug: TAK-659 |
| TAK-659 DLBCL (Dose Expansion) | Experimental | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with diffuse large B-cell lymphoma (DLBCL) (up to 49 cycles). Receives: Drug: TAK-659 |
| TAK-659 iNHL (Dose Expansion) | Experimental | Single dose TAK-659 100 mg, tablet, orally in pharmacokinetic (PK) Run-in prior to Cycle 1 followed by TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with indolent non-hodgkin lymphoma (iNHL) (up to 32 cycles). Receives: Drug: TAK-659 |
| TAK-659 MCL (Dose Expansion) | Experimental | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with mantle cell lymphoma (MCL) (up to 6 cycles). Receives: Drug: TAK-659 |
| TAK-659 PTLD (Dose Expansion) | Experimental | TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with post-transplant lymphoproliferative disorder (PTLD) (up to 1 cycle). Receives: Drug: TAK-659 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Dose Limiting toxicities (DLTs) in Cycle 1
DLT was defined as one of the following adverse events considered by the investigator to be possibly related to study drug: Grade 4 neutropenia unresolved to ≤Grade 1 or baseline >7 days in absence of growth factor support;≥Grade 3 neutropenia with fever and/or infection; Grade 4 thrombocytopenia unresolved to ≤ Grade 1 or baseline >7 days or a platelet count <10,000/mm^3; ≥Grade 3 thrombocytopenia with clinically significant bleeding; Grade 4 anemia; ≥Grade 3 nonhematological toxicity except (nausea and/or vomiting or diarrhea that has not resolved after 48 hours of treatment, transient fatigue, asymptomatic lipase elevation in absence of amylase elevation, asymptomatic elevation of a single liver enzyme in absence of bilirubin elevation);Inability to administer at least 75% of planned doses of study drug within Cycle 1;TAK-659-related nonhematologic toxicities ≥Grade 2 that required dose reduction or therapy discontinuation.
Measured: 28-day Cycle
Number of participants with Adverse events (AEs), Grade 3 and 4 AEs, Serious Adverse events (SAEs), Discontinuations for AEs
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.
Measured: First dose of study drug through 28 days after the last dose of study drug (Up to 49 months )
Secondary outcomes (8)
Overall response rate (ORR) in the CLL, DLBCL, iNHL, MCL, and PTLD Cohorts
Measured: Start of study drug treatment through Days 22 to 29 of Cycles 2,at end of every even numbered Cycle through 12,at end of every 4cycles through 24,at end of every 6 Cycles thereafter until disease progression or start of alternative therapies,End of Study
Duration of response (DOR), time to progression (TTP) and progression-free survival (PFS) in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Measured: Start of study drug treatment through Days 22 to 29 of Cycles 2, even numbered Cycle through 12,and at the end of every 4 cycles through 24, at the end of every 6 Cycles thereafter until disease progression or start of alternative therapies, End of Study
Overall Survival (OS) Rate in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Measured: Start of study drug treatment through last dose of study drug, then every 3 months until 12 months after first dosing of study drug if applicable, death, or the conclusion of the study, whichever occurs first (total duration of assessment up to 1 year)
Cmax: Maximum Observed Plasma Concentration for TAK-659
Measured: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659
Measured: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUC(0-24): Area under the Plasma Concentration-Time Curve from Time 0 to Time 24 hour for TAK-659
Measured: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUClast: Area under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-659
Measured: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
T1/2: Terminal Disposition Half-life
Measured: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2013 (estimated)
- Study start31 Dec 2013
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumor and Lymphoma MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02000934
- Sponsor's protocol ID
- C34001
- Other IDs
- U1111-1165-3590, 15/LO/0302
- Status last verified
- Feb 2023
- First submitted
- 18 Nov 2013
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Publications
Gordon LI, Karmali R, Kaplan JB, Popat R, Burris HA 3rd, Ferrari S, Madan S, Patel MR, Gritti G, El-Sharkawi D, Chau FI, Radford J, de Oteyza JP, Zinzani PL, Iyer SP, Townsend W, Miao H, Proscurshim I, Wang S, Katyayan S, Yuan Y, Zhu J, Stumpo K, Shou Y, Carpio C, Bosch F. Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659). Oncotarget. 2023 Jan 26;14:57-70. doi: 10.18632/oncotarget.28352.
PubMed 36702329Gordon LI, Kaplan JB, Popat R, Burris HA 3rd, Ferrari S, Madan S, Patel MR, Gritti G, El-Sharkawi D, Chau I, Radford JA, Perez de Oteyza J, Zinzani PL, Iyer S, Townsend W, Karmali R, Miao H, Proscurshim I, Wang S, Wu Y, Stumpo K, Shou Y, Carpio C, Bosch F. Phase I Study of TAK-659, an Investigational, Dual SYK/FLT3 Inhibitor, in Patients with B-Cell Lymphoma. Clin Cancer Res. 2020 Jul 15;26(14):3546-3556. doi: 10.1158/1078-0432.CCR-19-3239. Epub 2020 Apr 23.
PubMed 32327472
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-659 in Adult Patients With Advanced Solid Tumor and Lymphoma Malignancies
- ClinicalTrials.gov ID
- NCT02000934
- Acronym / sponsor ID
- C34001
- Keywords
- TAK-659, Solid Tumors, CLL, DLBCL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2013
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 4 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, multicenter, phase 1, dose escalation study of TAK-659 in adult participants with advanced solid tumor and lymphoma malignancies. This study will be the first to administer TAK-659 to humans. The participants population during dose escalation (Part A) will consist of adults previously diagnosed with any form of a solid tumor or lymphoma for which standard, curative, or life-prolonging treatment does not exist or is no longer effective. This first-in-human (FIH) study will include 5 dose expansion cohorts in refractory and/or relapsed Chronic Lymphocytic Leukemia (CLL), Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD) (Part B) following completion of dose escalation (Part A).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| TAK-659 60 mg (Dose Escalation) | Experimental | Drug: TAK-659TAK-659 60 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 49 cycles). |
| TAK-659 80 mg (Dose Escalation) | Experimental | Drug: TAK-659TAK-659 80 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 4 cycles). |
| TAK-659 100 mg (Dose Escalation) | Experimental | Drug: TAK-659TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 32 cycles). |
| TAK-659 120 mg (Dose Escalation) | Experimental | Drug: TAK-659TAK-659 120 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities (up to 41 cycles). |
| TAK-659 CCL (Dose Expansion) | Experimental | Drug: TAK-659TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with chronic lymphocytic leukemia (CCL) (up to 6 cycles). |
| TAK-659 DLBCL (Dose Expansion) | Experimental | Drug: TAK-659TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with diffuse large B-cell lymphoma (DLBCL) (up to 49 cycles). |
| TAK-659 iNHL (Dose Expansion) | Experimental | Drug: TAK-659Single dose TAK-659 100 mg, tablet, orally in pharmacokinetic (PK) Run-in prior to Cycle 1 followed by TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with indolent non-hodgkin lymphoma (iNHL) (up to 32 cycles). |
| TAK-659 MCL (Dose Expansion) | Experimental | Drug: TAK-659TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with mantle cell lymphoma (MCL) (up to 6 cycles). |
| TAK-659 PTLD (Dose Expansion) | Experimental | Drug: TAK-659TAK-659 100 mg, tablet, orally, once daily in 28-day cycles until disease progression or unacceptable toxicities in participants with post-transplant lymphoproliferative disorder (PTLD) (up to 1 cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Each participant must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female participants 18 years or older.
- To be enrolled to the dose escalation (Part A), participants must have
- To be enrolled to the dose expansion cohorts (Part B), participants must meet the following criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Key exclusion criteria (13 listed)
- Participants meeting any of the following exclusion criteria are not to be enrolled in the study.
- Participants with brain metastasis, or participants with central nervous system (CNS) lymphoma or participants with another malignancy within two years of study start, with exceptions as described in the protocol.
- 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.
- Life-threatening illness unrelated to cancer; major surgery within 14 days before the first dose of study drug; systemic infection requiring intravenous (IV) antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
- Female participants who are pregnant or lactating.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-659TAK-659 tablet | Drug | TAK-659 100 mg (Dose Escalation), TAK-659 120 mg (Dose Escalation), TAK-659 60 mg (Dose Escalation), TAK-659 80 mg (Dose Escalation), TAK-659 CCL (Dose Expansion), TAK-659 DLBCL (Dose Expansion), TAK-659 MCL (Dose Expansion), TAK-659 PTLD (Dose Expansion), TAK-659 iNHL (Dose Expansion) |
Primary outcome
Percentage of Participants with Dose Limiting toxicities (DLTs) in Cycle 1
Time frame: 28-day Cycle
DLT was defined as one of the following adverse events considered by the investigator to be possibly related to study drug: Grade 4 neutropenia unresolved to ≤Grade 1 or baseline >7 days in absence of growth factor support;≥Grade 3 neutropenia with fever and/or infection; Grade 4 thrombocytopenia unresolved to ≤ Grade 1 or baseline >7 days or a platelet count <10,000/mm^3; ≥Grade 3 thrombocytopenia with clinically significant bleeding; Grade 4 anemia; ≥Grade 3 nonhematological toxicity except (nausea and/or vomiting or diarrhea that has not resolved after 48 hours of treatment, transient fatigue, asymptomatic lipase elevation in absence of amylase elevation, asymptomatic elevation of a single liver enzyme in absence of bilirubin elevation);Inability to administer at least 75% of planned doses of study drug within Cycle 1;TAK-659-related nonhematologic toxicities ≥Grade 2 that required dose reduction or therapy discontinuation.
Number of participants with Adverse events (AEs), Grade 3 and 4 AEs, Serious Adverse events (SAEs), Discontinuations for AEs
Time frame: First dose of study drug through 28 days after the last dose of study drug (Up to 49 months )
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.
8 secondary outcomes
Overall response rate (ORR) in the CLL, DLBCL, iNHL, MCL, and PTLD Cohorts
Time frame: Start of study drug treatment through Days 22 to 29 of Cycles 2,at end of every even numbered Cycle through 12,at end of every 4cycles through 24,at end of every 6 Cycles thereafter until disease progression or start of alternative therapies,End of Study
Duration of response (DOR), time to progression (TTP) and progression-free survival (PFS) in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Time frame: Start of study drug treatment through Days 22 to 29 of Cycles 2, even numbered Cycle through 12,and at the end of every 4 cycles through 24, at the end of every 6 Cycles thereafter until disease progression or start of alternative therapies, End of Study
Overall Survival (OS) Rate in the CLL, DLBCL, iNHL, MCL, PTLD Cohorts
Time frame: Start of study drug treatment through last dose of study drug, then every 3 months until 12 months after first dosing of study drug if applicable, death, or the conclusion of the study, whichever occurs first (total duration of assessment up to 1 year)
Cmax: Maximum Observed Plasma Concentration for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUC(0-24): Area under the Plasma Concentration-Time Curve from Time 0 to Time 24 hour for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
AUClast: Area under the Plasma Concentration-Time Curve from Time 0 to Time of the Last Quantifiable Concentration for TAK-659
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
T1/2: Terminal Disposition Half-life
Time frame: Dose escalation: Cycle 1 Days 1 and 15 predose and multiple timepoints up to 24 hours postdose; PK Run-in Phase of the indolent NHL expansion cohort: predose and multiple timepoints up to 168 hours after a single dose prior to Cycle 1 Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Derived from this study: PubMed 36702329Gordon LI, Karmali R, Kaplan JB, Popat R, Burris HA 3rd, Ferrari S, Madan S, Patel MR, Gritti G, El-Sharkawi D, Chau FI, Radford J, de Oteyza JP, Zinzani PL, Iyer SP, Townsend W, Miao H, Proscurshim I, Wang S, Katyayan S, Yuan Y, Zhu J, Stumpo K, Shou Y, Carpio C, Bosch F. Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659). Oncotarget. 2023 Jan 26;14:57-70. doi: 10.18632/oncotarget.28352.
- Derived from this study: PubMed 32327472Gordon LI, Kaplan JB, Popat R, Burris HA 3rd, Ferrari S, Madan S, Patel MR, Gritti G, El-Sharkawi D, Chau I, Radford JA, Perez de Oteyza J, Zinzani PL, Iyer S, Townsend W, Karmali R, Miao H, Proscurshim I, Wang S, Wu Y, Stumpo K, Shou Y, Carpio C, Bosch F. Phase I Study of TAK-659, an Investigational, Dual SYK/FLT3 Inhibitor, in Patients with B-Cell Lymphoma. Clin Cancer Res. 2020 Jul 15;26(14):3546-3556. doi: 10.1158/1078-0432.CCR-19-3239. Epub 2020 Apr 23.
- Individual participant dataSharing planned: Yes. Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAK-659 in people with Advanced Solid Tumor and Lymphoma Malignancies, run by Calithera Biosciences, Inc at 15 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Italy, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Dose Limiting toxicities (DLTs) in Cycle 1 (time frame: 28-day Cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02000934, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.