Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients

NCT02435849 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCTL019B22022013-003205-25
• Study Type: interventional
• Target: 80
• Locations: 10 countries
• Sites: 22

Brief Summary

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Pediatric; ALL; Cell therapy; Lymphoblastic Leukemia; Acute; High Risk; Childhood; CTL019; tisagenlecleucel; Pediatric patients; r/r B-cell ALL; high risk B-cell ALL at first relapse; high risk B-cell ALL that relapsed < 6 months post allo-HSCT

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment.

  Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Platelets \>100 x 10\^9/L and Circulating blasts \<1% and No evidence of extramedullary disease, at least 7 days transfusion independency. CRi is defined as all the prior criteria being met, except that the following exists: Neutrophils ≤1.0 x 10\^9/L, and/or Platelets ≤100 x 10\^9/L, and/or Platelet and/or neutrophil transfusions ≤7 days before the date of the peripheral blood sample for disease assessment.

  during the 3 months after tisagenlecleucel administration

Secondary Outcomes (33)

• Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary)

  3 months after tisagenlecleucel administration

• Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary)

  3 months after tisagenlecleucel administration

• Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary)

  3 months after tisagenlecleucel administration

• Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT)

  6 months after tisagenlecleucel administration

• Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse

  6 months

Study Arms (1)

Single dose of CTL019

EXPERIMENTAL

Pediatric patients with relapsed or refractory B-cell ALL who were treated with single dose of tisagenlecleucel (CTL019).

Biological: CTL019

Interventions

CTL019 BIOLOGICAL

Tisagenlecleucel was administered as a single iv infusion. Dose: 2.0 to 5.0x10\^6 tisagenlecleucel per kg body weight (for patients ≤ 50 kg) or 1.0 to 2.5x10\^8 tisagenlecleucel (for patients \>50 kg).

Single dose of CTL019

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Relapsed or refractory pediatric B-cell ALL
• Adequate organ function
• For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry.
• Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
• Life expectancy \> 12 weeks.
• Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening
• Signed written informed consent and assent forms
• Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product
• Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.
• Cohort 1 only:
• First relapse AND hypodiploid cytogenetics OR
• First relapse AND t(17;19) with defined TCF3-HLF fusion OR
• First relapse with any cytogenetics provided the relapse occurred ≤ 36 months of initial diagnosis AND MRD at end of reinduction therapy is ≥0.01% by flow cytometry (local assessment)

You may not qualify if:

• Isolated extra-medullary disease relapse
• Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
• Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell \[sIg positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation)
• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
• Treatment with any prior gene therapy product
• Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
• Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
• Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
• Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).
• Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.
• Patient has an investigational medicinal product within the last 30 days prior to screening.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, defined as physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception for at least 12 months after the CTL019 infusion and after CAR T-cells are no longer present by qPCR on two consecutive tests
• Sexually active males must use a condom during intercourse at least 12 months after the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive tests

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Childrens Hospital Los Angeles SC CTL019

Los Angeles, California, 90027, United States

Location

Stanford Universtiy Medical Center SC - CTL019B2205J - B2206

Stanford, California, 94304, United States

Location

Children's Healthcare of Atlanta SC CTL019

Atlanta, Georgia, 30342, United States

Location

University of Michigan .

Ann Arbor, Michigan, 48109-2800, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children s Mercy Hospital SC - CTL019B2205J

Kansas City, Missouri, 64108, United States

Location

Duke Unversity Medical Center .

Durham, North Carolina, 27705, United States

Location

Oregon Health and Science University Doernbecher Children's Hosp.

Portland, Oregon, 97239-3098, United States

Location

The Childrens Hospital of Philadelphia CHOP

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Southwestern Medical Center .

Dallas, Texas, 75235, United States

Location

University of Utah Clinical Trials Office SC - CTL019B2205J

Salt Lake City, Utah, 84108, United States

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Vienna, A 1090, Austria

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

Novartis Investigative Site

Paris, Cedex 10, 75475, France

Location

Novartis Investigative Site

Paris, 75019, France

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Kyoto, 606 8507, Japan

Location

Novartis Investigative Site

Oslo, 0424, Norway

Location

Novartis Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Related Publications (7)

• Laetsch TW, Maude SL, Rives S, Hiramatsu H, Bittencourt H, Bader P, Baruchel A, Boyer M, De Moerloose B, Qayed M, Buechner J, Pulsipher MA, Myers GD, Stefanski HE, Martin PL, Nemecek E, Peters C, Yanik G, Khaw SL, Davis KL, Krueger J, Balduzzi A, Boissel N, Tiwari R, O'Donovan D, Grupp SA. Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial. J Clin Oncol. 2023 Mar 20;41(9):1664-1669. doi: 10.1200/JCO.22.00642. Epub 2022 Nov 18.

  PMID: 36399695 DERIVED

• Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022 Jun;36(6):1508-1515. doi: 10.1038/s41375-022-01550-z. Epub 2022 Apr 14.

  PMID: 35422096 DERIVED

• Thudium Mueller K, Grupp SA, Maude SL, Levine JE, Pulsipher MA, Boyer MW, August KJ, Myers GD, Tam CS, Jaeger U, Foley SR, Borchmann P, Schuster SJ, Waller EK, Awasthi R, Potthoff B, Warren A, Waldron ER, McBlane F, Chassot-Agostinho A, Laetsch TW. Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Blood Adv. 2021 Dec 14;5(23):4980-4991. doi: 10.1182/bloodadvances.2020003844.

  PMID: 34432863 DERIVED

• Levine JE, Grupp SA, Pulsipher MA, Dietz AC, Rives S, Myers GD, August KJ, Verneris MR, Buechner J, Laetsch TW, Bittencourt H, Baruchel A, Boyer MW, De Moerloose B, Qayed M, Davies SM, Phillips CL, Driscoll TA, Bader P, Schlis K, Wood PA, Mody R, Yi L, Leung M, Eldjerou LK, June CH, Maude SL. Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. J Immunother Cancer. 2021 Aug;9(8):e002287. doi: 10.1136/jitc-2020-002287.

  PMID: 34353848 DERIVED

• Buechner J, Grupp SA, Hiramatsu H, Teachey DT, Rives S, Laetsch TW, Yanik GA, Wood P, Awasthi R, Yi L, Chassot-Agostinho A, Eldjerou LK, De Moerloose B. Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy. Blood Adv. 2021 Jan 26;5(2):593-601. doi: 10.1182/bloodadvances.2020002757.

  PMID: 33496754 DERIVED

• Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1710-1718. doi: 10.1016/S1470-2045(19)30493-0. Epub 2019 Oct 9.

  PMID: 31606419 DERIVED

• Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.

  PMID: 29385370 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

tisagenlecleucel

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2015
• First Posted: May 6, 2015
• Study Start: April 8, 2015
• Primary Completion: January 21, 2020
• Study Completion: November 17, 2022
• Last Updated: February 13, 2024
• Results First Posted: November 22, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

JP (1); ES (1); US (11); FR (2); IT (1); AU (1); BE (1); NO (1); DE (1); CA (2)