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A Study of TAK-007 in Adults With Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05020015
Recruitment Status : Recruiting
First Posted : August 25, 2021
Last Update Posted : December 28, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE August 20, 2021
First Posted Date  ICMJE August 25, 2021
Last Update Posted Date December 28, 2022
Actual Study Start Date  ICMJE November 22, 2021
Estimated Primary Completion Date October 26, 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2021)
  • Part 1: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 60 months ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
  • Part 1: Number of Participants with Clinically Significant Changes in Laboratory Parameters [ Time Frame: Up to 60 months ]
    Laboratory parameters will include hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.
  • Part 1: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: Up to 60 months ]
    Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse rate (bpm).
  • Part 2: Overall Response Rate (ORR) per Independent Review Committee (IRC) [ Time Frame: Up to 60 months ]
    ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as best response to treatment, determined by the IRC per the Lugano 2014 criteria after TAK-007 administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2021)
  • Part 1 and Part 2: ORR per Investigator [ Time Frame: Up to 60 months ]
    ORR is defined as the percentage of participants with CR or PR as best response to treatment, determined by the investigator per the Lugano 2014 criteria after TAK-007 administration.
  • Part 1 and Part 2: Complete Response (CR) per Investigator [ Time Frame: Up to 60 months ]
    CR will be defined per Lugano 2014 criteria as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease.
  • Part 2: Complete Response (CR) Per IRC [ Time Frame: Up to 60 months ]
    CR will be defined per Lugano criteria as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease.
  • Part 1 and Part 2: Duration of Response (DOR) per Investigator [ Time Frame: Up to 60 months ]
    DOR is defined as the time from the date of first documented objective response to the date of first documented disease progression, determined by investigator per Lugano 2014 criteria classification or death, whichever comes first, for participants who experience an objective response.
  • Part 2: Duration of Response (DOR) per IRC [ Time Frame: Up to 60 months ]
    DOR is defined as the time from the date of first documented objective response to the date of first documented disease progression, determined by the IRC Lugano 2014 criteria classification or death, whichever comes first, for participants who experience an objective response.
  • Part 1 and Part 2: Progression-free Survival (PFS) per Investigator [ Time Frame: Up to 60 months ]
    PFS is defined as time from enrollment date to the date of disease progression, determined by the investigator per Lugano 2014 criteria classification or death from any cause, whichever comes first.
  • Part 2: Progression-free Survival (PFS) per IRC [ Time Frame: Up to 60 months ]
    PFS is defined as time from enrollment date to the date of disease progression, determined by the IRC per Lugano 2014 criteria classification or death from any cause, whichever comes first.
  • Parts 1 and 2: Overall Survival (OS) [ Time Frame: Up to 60 months ]
    OS is defined as time from enrollment to the date of death from any cause.
  • Part 2: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 60 months ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
  • Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters [ Time Frame: Up to 60 months ]
    Laboratory parameters will include hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.
  • Part 2: Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: Up to 60 months ]
    Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
  • Parts 1 and 2: Cmax - Maximum Observed Blood Concentration of TAK-007 [ Time Frame: Predose (Day 0) and at multiple timepoints postdose (up to 60 months) ]
  • Parts 1 and 2: Tmax - Time of First Occurrence of Cmax of TAK-007 [ Time Frame: Predose (Day 0) and at multiple timepoints postdose (up to 60 months) ]
  • Parts 1 and 2: Tlast - Time of Last Measurable Concentration Above the Lower Limit of Quantitation of TAK-007 [ Time Frame: Predose (Day 0) and at multiple timepoints postdose (up to 60 months) ]
  • Parts 1 and 2: AUClast - Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of TAK-007 [ Time Frame: Predose (Day 0) and at multiple timepoints postdose (up to 60 months) ]
  • Part 1 and Part 2: Concentration of Interleukin (IL)-15 and Other Soluble Immune Factors in Plasma Over Time [ Time Frame: Up to 24 months ]
    Concentration of IL-15 and soluble immune factors (eg, Interferon (IFN)-gamma (γ), IL-1 beta (β), IL- 2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, Tumor necrosis factor (TNF) alpha (α), Granulocyte-macrophage colony-stimulating factor (GM-CSF)) in plasma over time will be reported.
  • Percentage of Participants with B-cell Aplasia Before and After TAK-007 Administration [ Time Frame: Up to 24 months ]
  • Percentage of Participants with Detectable Anti-human Leukocyte Antigen (HLA) and Anti-chimeric Antigen Receptor (CAR) Antibodies Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time [ Time Frame: Up to 24 months ]
  • Percentage of Participants with Positive Replication Competent Retrovirus (RCR) Test Results Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time [ Time Frame: Up to 60 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of TAK-007 in Adults With Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)
Official Title  ICMJE A Phase 2, Open-label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Brief Summary

This study has 2 parts.

The main aim of Part 1 is to check for side effects from TAK-007 in adults with relapsed or refractory B-cell Non-Hodgkin Lymphoma.

The main aim of Part 2 is to learn if lymphomas are reduced or gone after treatment withTAK-007 in adults with relapsed or refractory B-cell Non-Hodgkin Lymphoma or indolent non-Hodgkin lymphoma (iNHL).

Participants will receive lymphodepleting chemotherapy for 3 days before receiving a single injection of TAK-007. After this, participants will regularly visit the clinic for check-ups.

Detailed Description

The product being tested in this study is called TAK-007. TAK-007 is being tested to evaluate the safety and tolerability in adult participants with r/r B-cell NHL. The study will include 2 parts: Part 1 (Dose escalation and dose expansion) and Part 2.

The study will enroll approximately 242 patients.

In Part 1, dose escalation and dose expansion cohorts participants will receive TAK-007 as follows:

  • Part 1: Dose escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells (±30%)
  • Part 1: Dose escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells (±25%)
  • Part 1: Dose expansion: r/r LBCL: TAK-007 - 200×10^6/800×10^6 Viable NK Cells
  • Part 1: Dose expansion: r/r iNHL: TAK-007 - 200×10^6/ 800×10^6 Viable NK Cells

Based on the data in Part 1, a single TAK-007 dose level will be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D).

Once RP2D is determined, participants will be enrolled in Part 2 of the study in the following cohorts:

  • Cohort 1: TAK-007 (LBCL)
  • Cohort 2: TAK-007 (iNHL)

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic and will enroll in a separate, long-term, follow-up study for continued safety assessments for up to 15 years after TAK-007 administration.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This study has 2 Parts: Part 1 is composed of dose escalation followed by dose expansion and Part 2.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)
Intervention  ICMJE
  • Biological: TAK-007
    TAK-007 intravenous injection.
  • Drug: Chemotherapy Agents
    Fludarabine and cyclophosphamide as per standard of care.
Study Arms  ICMJE
  • Experimental: Part 1: Dose Escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells
    Participants will receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 200×10^6 anti-CD19 chimeric antigen receptor (CD19-CAR+) viable natural killer (NK) cells, single-dose, intravenously, once on Day 0.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
  • Experimental: Part 1: Dose Escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells
    Participants will receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells, single-dose, intravenously, once on Day 0.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
  • Experimental: Part 1: Dose Expansion: LBCL: TAK-007 - 200×10^6/ 800×10^6 CD19-CAR+ Viable NK Cells
    Participants with r/r Large B-cell Lymphoma (LBCL) will receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 - 200×10^6/ 800×10^6 CD19-CAR+ Viable NK Cells, single-dose, intravenously, once on Day 0 to determine RP2D.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
  • Experimental: Part 1: Dose Expansion: iNHL: TAK-007 - 200×10^6/ 800×10^6 CD19-CAR+ Viable NK Cells
    Participants with r/r Indolent Non-Hodgkin Lymphoma (iNHL) will receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 - 200×10^6/ 800×10^6 CD19-CAR+ Viable NK Cells, single-dose, intravenously, once on Day 0 to determine RP2D.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
  • Experimental: Part 2: Cohort 1- LBCL
    Participants with LBCL will be enrolled in this cohort to receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 at RP2D, intravenously, once on Day 0.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
  • Experimental: Part 2: Cohort 2- iNHL
    Participants with iNHL will be enrolled in this cohort to receive lymphodepleting chemotherapy per day intravenously followed by TAK-007 at RP2D, intravenously, once on Day 0.
    Interventions:
    • Biological: TAK-007
    • Drug: Chemotherapy Agents
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 20, 2021)
242
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 26, 2029
Estimated Primary Completion Date October 26, 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Participants who have a life expectancy ≥12 weeks.
  2. Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  3. Participants with a diagnosis of previously treated r/r histologically proven Cluster of Differentiation (CD)19 expressing disease of the following types:

    a. LBCL, including the following subtypes defined by the World Health Organization (WHO): i. Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS). ii. High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangement iii. HGBL NOS without translocations. iv. DLBCL arising from iNHL including follicular lymphoma (FL) or marginal zone lymphoma (MZL).

    v. T-cell/histiocyte-rich LBCL. vi. DLBCL associated with chronic inflammation. vii. Epstein-Barr virus-positive DLBCL-NOS. viii. Primary cutaneous DLBCL, leg type. ix. Primary mediastinal large B-cell lymphoma (PMBCL). x. FL Grade 3B. b. iNHL, including the following subtypes defined by the WHO: i. FL Grades 1, 2, 3A. ii. MZL (nodal, extranodal, and splenic).

  4. Participants who have measurable disease, defined as at least 1 lesion per the Lugano classification. Lesions situated in a previously irradiated area are considered measurable if radiographic progression has been documented in such lesions following completion of radiation therapy. LBCL should have positron emission tomography -positive disease per the Lugano classification.
  5. Participants whose disease is r/r after at least 2 prior lines of systemic therapy:

    1. Participants with r/r LBCL must have received an anti-CD20 monoclonal antibody (mAb) and an anthracycline containing chemotherapy regimen and failed or be ineligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT).
    2. Participants with iNHL must have received an anti-CD20 mAb and an alkylating agent (eg, bendamustine or cyclophosphamide).
    3. Preinduction salvage chemotherapy and ASCT should be considered 1 therapy.
    4. Any consolidation/maintenance therapy after a chemotherapy regimen (without intervening relapse) should be considered 1 line of therapy with the preceding combination therapy. Maintenance antibody therapy should not be considered a line of therapy.
    5. Single-agent anti-CD20 mAb therapy should not be considered a line of therapy.
  6. Participants who have adequate bone marrow function defined as follows:

    1. Absolute neutrophil count >500/μL.
    2. Platelet count of >50,000/μL at screening. Participants with transfusion-dependent thrombocytopenia are excluded.
  7. Participants who have adequate renal, hepatic, cardiac, and pulmonary function as defined in the study protocol:

    1. Estimated glomerular filtration rate (GFR; Modification of Diet in Renal Disease equation [MDRD]) ≥30 mL/min.
    2. Serum alanine aminotransferase/aspartate aminotransferase ≤5 times the upper limit of normal range (ULN), as long as participant is asymptomatic.
    3. Total bilirubin ≤2 mg/dL. Participants with Gilbert's syndrome may have a bilirubin level >2 × ULN, per discussion between the investigator and the medical monitor.
    4. Left ventricular ejection fraction (LVEF) ≥40% as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed within 1 month of determination of eligibility.
    5. No evidence of clinically relevant pericardial effusion, and no acute clinically significant electrocardiogram (ECG) findings.
    6. Absence of Grade ≥2 pleural effusion. Grade 1 stable pleural effusions are allowed.
    7. Baseline oxygen saturation >92% on room air.
  8. Participants are required to consent to provide either sufficient archived formalin-fixed paraffin embedded (at least 10 unstained slides, ideally 20 unstained slides) or fresh tumor tissue obtained after the last relapse (see laboratory manual for details). Exception may be granted by sponsor medical monitor per discussion with investigator.

Exclusion Criteria:

  1. Participants with total body weight of <40 kg.
  2. Participants with primary or secondary central nervous system (CNS) involvement by lymphoma. Participants with a history of secondary CNS involvement by lymphoma without evidence of CNS involvement at screening may be included.
  3. Participants with Burkitt lymphoma, mantle cell lymphoma, lymphoplasmocytic lymphoma, or transformation from CLL/small lymphocytic lymphoma (Richter transformation).
  4. Participants with a history of malignancy other than nonmelanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast), low-grade tumors deemed to be cured and not treated with systemic therapy (eg, by gastro-endoscopy curatively removed gastric cancer) or unless disease free for ≥3 years at screening.
  5. Participants who have undergone autologous or allogeneic transplant or Chimeric antigen receptor T cells (CAR-T) therapy within 3 months of planned enrollment. Participants after allogeneic transplant have to be off systemic immunosuppressive therapy and without the evidence of clinically relevant acute or chronic graft-versus-host disease (GvHD) at the time of enrollment.
  6. Treatment with any investigational products or any systemic anticancer treatment within 14 days or 2 half-lives of the treatment (whichever is longer) before conditioning therapy.
  7. Participants with active infection, including fungal, bacterial, viral, or other infection that is uncontrolled or requires IV antimicrobials for management within 3 days before enrollment.
  8. Participants with a history or presence of active or clinically relevant CNS disorder, such as seizure, encephalopathy, cerebrovascular ischemia/hemorrhage, severe dementia, cerebellar disease, or any autoimmune disease with CNS involvement. For CNS disorders that recover or are in remission, participants without recurrence within 2 years of planned study enrollment may be included.
  9. Participants with any of the following within 6 months of enrollment: myocardial infarction, cardiac angioplasty or stenting, unstable angina, symptomatic congestive heart failure (ie, New York Heart Association Class II or greater), clinically significant arrythmia (including uncontrolled atrial fibrillation), or any other clinically significant cardiac disease.
  10. Participants who have received a live vaccine ≤6 weeks before the start of the conditioning regimen.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05020015
Other Study ID Numbers  ICMJE TAK-007-2001
2021-002086-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/
Current Responsible Party Takeda
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Takeda
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP