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Lymphoma, Non-HodgkinPhase 1NCT03772288

A Study of TAK-659 in Combination With NKTR-214 in Participants With Advanced Non-Hodgkin Lymphoma (NHL)

A Phase 1 study testing TAK-659 and NKTR-214 in people with Lymphoma, Non-Hodgkin, run by Calithera Biosciences, Inc at 6 sites in 2 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TAK-659 when administered in combination with NKTR-214. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
TAK-659 and NKTR-214
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
6 sitesin 2 countries
Study dates
3 Apr 2019to 17 Nov 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

  • Histologically or cytologically confirmed diagnosis of advanced B-cell NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) (Waldenstrom macroglobulinemia [WM] and chronic lymphocytic leukemia [CLL]/small lymphocytic leukemia [SLL] are excluded).
  • Radiographically or clinically measurable disease with at least 1 target lesion per (greater than [>] 1.5 centimeter [cm] in the longest diameter for a lymph node or nodal mass, or >1.0 cm in the longest diameter for extranodal disease) Lugano 2014 criteria for malignant lymphoma.
  • Participants who are refractory or relapsed after at least 2 prior lines of therapy due to progression, intolerance, or physician/participant decision, and for whom no effective standard therapy is available per the investigator's assessment. The sponsor may restrict prior lines of therapy in the expansion phase of the study based on emerging data. The decision may be documented and shared with investigators in a memo before the initiation of the dose expansion phase followed by updating the exclusion criteria in a subsequent amendment, if deemed necessary. Requirements for prior therapy depending on disease type are outlined in the protocol, however all patients must be ineligible for or have already failed hematopoietic stem cell transplant.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and life expectancy of >3 months.
  • Must have adequate organ function.
  • Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the clinically significant reversible effects of prior anticancer therapy.

Who cannot join

  • 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. 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 AEs.
  • Known human immunodeficiency virus (HIV) infection or HIV-related malignancy, hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
  • 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.
  • Systemic anticancer treatment (including investigational agents) or radiotherapy less than 2 weeks before the first dose of study treatment (<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; <=8 weeks for cell-based therapy or antitumor vaccine).
  • Participants in need of immediate cytoreductive therapy.
  • Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery, defined by the entry criteria in the study, before Cycle 1 Day 1 or allogeneic stem cell transplant any time.
Show all 16Show fewer
  • Use or consumption of:
  • Medications or supplements that are known to be inhibitors of P-glycoprotein (P-gp) and/or strong reversible inhibitors of cytochrome (CYP3A), strong CYP3A mechanism-based inhibitors, strong CYP3A inducers or P-gp inducers within 5 times the inhibitor half-life or within 7 days 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.
  • 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.
  • Active, known, or suspected autoimmune disease. Participants requiring systemic treatment within the past 3 months or with a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient taking 10 mg or less of prednisone or equivalent, participants with vitiligo, hypothyroidism stable on hormone replacement, type 1 diabetes, Graves disease, Hashimoto disease, alopecia areata, eczema, or with medical monitor approval.)
  • History of organ or tissue transplant that requires systemic use of immunosuppressive agents.
  • Prior treatment with TAK-659 or any spleen tyrosine kinase (SYK) inhibitor or interleukin-2 (IL-2) therapy.
  • Use of >2 antihypertensive medications for management of hypertension (including diuretics).
  • Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery or systemic infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  • 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.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States3 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • New York University Langone Medical Center

    New York, New York, 10016

Other trials in United States

Canada3 sites

  • Alberta Health Services

    Calgary, Alberta, T2N 2T9

  • Jewish General Hospital

    Montreal, Quebec, H3T1E2

  • Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de lEstrie - CHUS)

    Sherbrooke, Quebec, J1H 5N3

Other trials in Canada

About this study

Official title: A Phase 1b Study of TAK-659 in Combination With NKTR-214 in Patients With Advanced Non-Hodgkin Lymphoma

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TAK-659 when administered in combination with NKTR-214.

Read the detailed description

The drugs that are being tested in this study are TAK-659 and NKTR-214. TAK-659 in combination with NKTR-214 is being tested for participants with advanced B-cell NHL, including DLBCL, FL, MZL, or MCL, after 2 prior lines of therapy. The study will determine the MTD or the RP2D of TAK-659 when administered with NKTR-214.

The study will enroll approximately 40 participants, approximately 18 to 24 participants in a dose escalation phase, and approximately 12 participants will be added after determination of MTD/RP2D in the safety expansion phase. This study consists of 2 phases: a dose escalation phase and a safety expansion phase.

TAK-659 and NKTR-214 doses will be escalated according to a modified 3+3 dose escalation schema. TAK-659 60 milligram (mg) + NKTR-214 0.003 milligram per kilogram (mg/kg) is the starting dose. Participants could also receive 80 mg once daily (QD) TAK-659 during dose escalation and 0.003mg/kg or 0.006mg/kg of NKTR-214. Lower doses (example 40 mg) and/or alternative regimens (including intermittent dosing) or schedules of TAK-659 are permissible following discussion between sponsor and investigators. In dose escalation phase, dose levels will be escalated based on available safety and tolerability data to determine the MTD or RP2D. Dose for safety expansion phase will be based on available safety, pharmacodynamics, and preliminary efficacy data.

For participants enrolled in either the dose escalation or safety expansion phases, the maximum duration of treatment will be 12 months unless, in the opinion of the investigator and with the agreement of the sponsor, the participant would derive benefit from continued therapy beyond 12 months. Participants will make multiple visits to the clinic, and will have an end of treatment visit 30 days after the last dose of TAK-659 or NKTR-214 or before the start of subsequent alternative anticancer therapy, whichever occurs first. Participants will be followed for 90 days after the last dose or subsequent anti-cancer therapy, whichever occurs first, to permit the detection of any delayed treatment-related adverse events (AEs).

Being tested
TAK-659, NKTR-214
Keywords
Drug Therapy
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-659Drug

    Tablets.

  • NKTR-214Drug

    Intravenous infusion.

Study groups in NCT03772288
Study groupRoleWhat they receive
Dose Escalation: TAK-659 + NKTR-214ExperimentalTAK-659 tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 in a 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participant. The dose escalation phase will determine the MTD or RP2D of TAK-659. Dose escalation of TAK-659 will be based on available safety and tolerability data.
Receives: Drug: TAK-659; Drug: NKTR-214
Safety Expansion: TAK-659 + NKTR-214ExperimentalTAK-659, tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 of 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participants. TAK-659 and NKTR-214 MTD/RP2D will be determined from the dose escalation phase.
Receives: Drug: TAK-659; Drug: NKTR-214

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of TAK-659 in Combination with NKTR-214

    Measured: 3 weeks after last dose of last participant in dose escalation or up to 6 months

  2. RP2D of TAK-659 in Combination with NKTR-214

    Measured: 3 weeks after last dose of last participant in dose escalation or up to 6 months

Secondary outcomes (9)

  1. Cmax: Maximum Observed Plasma Concentration for TAK-659

    Measured: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659

    Measured: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  3. AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659

    Measured: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  4. Cmax: Maximum Observed Plasma Concentration for NKTR-214

    Measured: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)

  5. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for NKTR-214

    Measured: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)

  6. AUC: Area Under the Plasma Concentration-time Curve for NKTR-214

    Measured: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)

  7. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants in the response-evaluable population who achieved either complete response (CR) or partial response (PR) as assessed by the investigator according to the Lugano 2014 criteria.

    Measured: Through study completion, approximately 40 months

  8. Duration of Response (DOR)

    DOR is defined as the time from first CR or PR to PD or relapse in the response-evaluable population.

    Measured: From first CR or PR to progressive disease (PD) or relapse (through study completion, approximately 40 months)

  9. Progression-free Survival (PFS)

    PFS is defined as the time from first dose to PD or death in the response-evaluable population.

    Measured: From first dose of study drug to PD or death (through study completion, approximately 40 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2018
  2. Study start3 Apr 2019
  3. Primary completion10 Nov 2021 (estimated)
  4. Study completion17 Nov 2021 (estimated)

Why it stopped: Business Decision: No Safety or Efficacy Concerns

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03772288
Sponsor's protocol ID
C34015
Other IDs
U1111-1218-4372
Status last verified
Feb 2023
First submitted
10 Dec 2018
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-659 and NKTR-214 in people with Lymphoma, Non-Hodgkin, run by Calithera Biosciences, Inc at 6 sites in 2 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 6 inclusion and 16 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: withdrawn, 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 6 sites in United States, Canada. 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 was withdrawn before enrolling participants, so there are no results.

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?

MTD of TAK-659 in Combination with NKTR-214 (time frame: 3 weeks after last dose of last participant in dose escalation or up to 6 months). 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 NCT03772288.

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.

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