ZUMA-2: Study to Evaluate the Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)

• Sponsor: Kite, A Gilead Company (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04880434
• Collaborator: (none)
• Enrollment: 90
• Locations: 42
• Arm: 1
• Anticipated Duration (Months): 209.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective is to evaluate the efficacy of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL) in Cohort 3 of this study.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Mantle Cell Lymphoma	Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Brexucabtagene autoleucel	Phase 2

Detailed Description

Study KTE-C19-102 (NCT02601313) enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.

The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, this separate registration is only for Cohort 3.

After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma
• Actual Study Start Date: Apr 27, 2021
• Anticipated Primary Completion Date: Jul 1, 2024
• Anticipated Study Completion Date: Oct 1, 2038

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Brexucabtagene autoleucel (KTE-X19) Participants with relapsed/refractory mantle cell lymphoma will receive conditioning chemotherapy consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg, with a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 3.

Drug: Fludarabine; Administered intravenously; Drug: Cyclophosphamide; Administered intravenously; Biological: Brexucabtagene autoleucel; A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells; Other Names: KTE-X19 TECARTUS™

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC) [Up to 2 years]

   ORR is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification as determined by IRRC.

Secondary Outcome Measures

1. Duration of Response (DOR) [Up to 7 years]

   DOR is defined as the time from their first objective response to disease progression or death.

2. Percentage of Participants With Best Objective Response (BOR) [Up to 7 years]

   Best objective response is defined as the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable as best response to treatment.

3. Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators [Up to 7 years]

   ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification.

4. Progression Free Survival (PFS) [Up to 7 years]

5. Overall Survival [Up to 7 years]

6. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [Up to 7 years]

7. Percentage of Participants With Clinically Significant Changes in Laboratory Values [Up to 7 years]

8. Percentage of Participants Who Develop Anti-CD19 CAR Antibodies [Up to 7 years]

9. Levels of Anti-CD19 CAR T Cells in Blood [Up to 7 years]

10. Levels of Cytokines in Serum [Up to 7 years]

11. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score [Baseline and up to 24 months]

    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline.

12. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score [Baseline and up to 24 months]

    EQ-5D is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ5D-VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicates better self-reported health status.

13. Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time [Baseline and up to 6 months]

    EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale; higher score indicate high QoL. A positive change from baseline indicates better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Up to 5 prior regimens for MCL. Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. Individuals must not have received prior therapy with a BTKi.

• At least 1 measurable lesion

• Platelet count ≥ 75,000/uL

• Creatinine clearance (as estimated by Cockcroft Gault) ≥ to 60 cc/min

• Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA), and no clinically significant electrocardiogram (ECG) findings

• Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). Individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing

• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement

• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	City of Hope	Duarte	California	United States	91010
3	Stanford University	Palo Alto	California	United States	94305
4	University California Los Angeles (UCLA)	Santa Monica	California	United States	90404
5	Sarah Cannon- Denver	Denver	Colorado	United States	80218
6	University of Miami	Miami	Florida	United States	33136
7	Moffitt Cancer Center	Tampa	Florida	United States	33612
8	Emory University	Atlanta	Georgia	United States	30322
9	University of Chicago	Chicago	Illinois	United States	60637
10	Loyola University Medical Center	Maywood	Illinois	United States	60153
11	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
13	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
14	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
15	University of Rochester	Rochester	New York	United States	14642
16	Duke University	Durham	North Carolina	United States	27710
17	Cleveland Clinic - Taussig Cancer Institute	Cleveland	Ohio	United States	44195
18	Ohio State University	Columbus	Ohio	United States	43220
19	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
20	Sarah Cannon - Tenessee	Nashville	Tennessee	United States	37203
21	Vanderbilt University	Nashville	Tennessee	United States	37232
22	Baylor Cancer Hospital	Dallas	Texas	United States	75246
23	MD Anderson Cancer Center	Houston	Texas	United States	77030
24	Swedish Cancer Institute	Seattle	Washington	United States	98104
25	CHU de Montpellier	Montpellier CEDEX 05		France	34295
26	Hospital Saint Louis	Paris		France	75010
27	Hopital Haut-Leveque	Pessac		France	44035
28	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
29	CHU de Rennes	Rennes		France	35033
30	Universitätsklinik Dresden	Dresden		Germany	01307
31	Johannes Gutenberg University Hospital-University Mainz	Mainz		Germany	55101
32	Munich University of Technology-Medical Faculty- Ethics Committee	München		Germany	81377
33	Universitaetsklinikum Wuerzburg	Wuerzburg		Germany	97080
34	Academisch Medisch Centrum	Amsterdam		Netherlands	1100
35	University Medical Center Groningen	Groningen		Netherlands	9700 RB
36	Erasmus MC	Rotterdam		Netherlands	3015 CE
37	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
38	Hospital Clinic Barcelona	Barcelona		Spain
39	Hospital Universitario de Salamanca	Salamanca		Spain	37007
40	Queen Elizabeth University Hospital	Glasgow		United Kingdom	G51 4TF
41	Kings College Hospital	London		United Kingdom	SE5 9RS
42	Manchester Royal Infirmary	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Kite, A Gilead Company

Investigators

• Study Director: Kite Study Director, Kite, A Gilead Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Gilead Clinical Trials Website

Publications

None provided.

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT04880434
• Other Study ID Numbers: KTE-C19-102 (Cohort 3); 2015-005008-27
• First Posted: May 10, 2021
• Last Update Posted: Jul 27, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Cyclophosphamide; Fludarabine

Study Results

No Results Posted as of Jul 27, 2022