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

NCT05020015 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: TAK-007-20012021-002086-18
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 15

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 (r/r) B-cell Non-Hodgkin Lymphoma (NHL), The main aim of Part 2 is to learn whether lymphoma disease responds to treatment with TAK-007 in adults with r/r B-cell NHL or iNHL. Participants will receive 3 days of chemotherapy to reduce a type of white blood cells called lymphocytes, in the blood. This is called lymphodepleting chemotherapy (LDC) or lymphodepletion. After LDC, patients will receive a single injection of TAK-007 or three weekly injections of TAK-007 (multi-dose injection). After this, participants will regularly visit the clinic for check-ups.

Conditions

Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)

Keywords

Drug Therapy; Chimeric antigen receptor; Natural killer cells; Cell therapy; Allogeneic

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  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 (e.g., 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. TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product.

  Up to 24 months

• Number of Participants With Clinically Significant Changes in Laboratory Parameters

  Laboratory parameters included hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.

  Up to 24 months

• Number of Participants With Notable Changes in Vital Signs

  Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant had rested for at least 5 minutes), and pulse rate (beats per minute \[bpm\]).

  Up to 24 months

Secondary Outcomes (13)

• ORR Per Investigator

  Up to 24 months

• Complete Response (CR) Per Investigator

  Up to 24 months

• Duration of Response (DOR) Per Investigator

  Up to 24 months

• Progression-free Survival (PFS) Per Investigator

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

Study Arms (4)

Dose Escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells

EXPERIMENTAL

Participants received lymphodepleting chemotherapy per day intravenously (IV) for 3 days followed by TAK-007 200×10\^6 anti-CD19 chimeric antigen receptor (CD19-CAR+) viable NK cells, single-dose, IV infusion, once on Day 0.

Biological: TAK-007; Drug: Chemotherapy Agents

Dose Escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells

EXPERIMENTAL

Participants received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 - 800×10\^6 CD19-CAR+ viable NK cells, single-dose, IV infusion, once on Day 0.

Biological: TAK-007; Drug: Chemotherapy Agents

Dose Expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells

EXPERIMENTAL

Participants with r/r LBCL received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 at the dose level selected based on the dose escalation part (800×10\^6 CD19-CAR+ viable NK cells), as a single-dose, IV infusion, once on Day 0 to determine recommended phase 2 dose (RP2D).

Biological: TAK-007; Drug: Chemotherapy Agents

Dose Expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells

EXPERIMENTAL

Participants with r/r iNHL received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 at the dose level(s) selected based on the dose escalation part (800×10\^6 CD19-CAR+ viable NK cells), as a single-dose, IV infusion, once on Day 0 to determine RP2D.

Biological: TAK-007; Drug: Chemotherapy Agents

Interventions

TAK-007 BIOLOGICAL

TAK-007 intravenous injection.

Dose Escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells; Dose Escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Dose Expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Dose Expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells

Chemotherapy Agents DRUG

Fludarabine and cyclophosphamide as per standard of care.

Dose Escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells; Dose Escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Dose Expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Dose Expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have a life expectancy ≥12 weeks.
• Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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).
• 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 (PET) -positive disease per the Lugano classification.
• Participants who have r/r LBCL or r/r iNHL after ≥2 prior lines of systemic therapy: (Expansion Cohorts 1A and 1B \[LBCL 3L+\], and 2A \[iNHL 3L +\]) or r/r LBCL after 1 prior line of systemic therapy (Expansion Cohort 1C \[LBCL 2L\]):
• 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).
• Participants with iNHL must have received an anti-CD20 mAb and an alkylating agent (eg, bendamustine or cyclophosphamide).
• Preinduction salvage chemotherapy and ASCT should be considered 1 line of therapy.
• 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.
• Single-agent anti-CD20 mAb therapy should not be considered a line of therapy.
• Bridging chemotherapy given just prior to CAR-T cell therapy treatment should be considered one line of therapy together with cell therapy.
• Participants who have received prior CD19-targeting CAR-T cell therapy must have achieved at least a partial response to the most recent CD19-targeting CAR-T cell therapy.
• Participants with 1 prior line of therapy in Part 1 Cohort 1C must have either:

You may not qualify if:

• Participants with total body weight of \<40 kg.
• 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.
• Participants with Burkitt lymphoma, mantle cell lymphoma, lymphoplasmocytic lymphoma, or transformation from CLL/small lymphocytic lymphoma (Richter transformation).
• 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.
• Participants who have undergone autologous or allogeneic transplant or Chimeric antigen receptor T cells (CAR-T) or Chimeric antigen receptor Natural Killer cells (CAR-NK) 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.
• 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. For rituximab, a half-life of 22 days should be considered.
• 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.
• 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.
• 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.
• Participants who have received a live vaccine ≤6 weeks before the start of the conditioning regime.

Sponsors & Collaborators

• Takeda: lead

Study Sites (15)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

MedStar Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Sylvester Comprehensive Cancer Center University of Miami Hospitals and Clinics

Miami, Florida, 33136, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

DUHS Duke Blood Cancer Center

Durham, North Carolina, 27705, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University Sidney Kimmer Cancer Center, Clinical Research Organization

Philadelphia, Pennsylvania, 19107, United States

Location

Saint Davids South Austin Medical Center

Austin, Texas, 78704, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
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MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study has 2 Parts: Part 1 is composed of dose escalation followed by dose expansion and Part 2.

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 25, 2021
• Study Start: November 12, 2021
• Primary Completion: June 16, 2024
• Study Completion (Estimated): December 20, 2038
• Last Updated: March 31, 2026
• Results First Posted: August 12, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (15)