Last Update: Mar 25, 2024
A Phase II Trial of Tisagenlecleucel in First-line High-risk (HR) Pediatric and Young Adult Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL) Who Are Minimal Residual Disease (MRD) Positive at the End of Consolidation (EOC) Therapy
ClinicalTrials.gov Identifier:
Novartis Reference Number:CCTL019G2201J
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, patient will have assessments performed more frequently in the first month and then at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Efficacy and safety will be assessed at study visits and as clinically indicated throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up safety will continue under a separate protocol per health authority guidelines.

B-Cell Acute Lymphoblastic Leukemia
Phase 2
Recruiting
120
Jun 24, 2019
Oct 19, 2027
All
1 Year - 25 Years (Child, Adult)

Interventions

Biological

CTL019

Based on the subject's weight, one of two possible dose ranges will be prepared for the subject: Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight OR Subjects > 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Eligibility Criteria

Inclusion Criteria:

CD19 expressing B-cell Acute Lymphoblastic Leukemia
De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
Age 1 to 25 years at the time of screening
Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%

Adequate organ function during the screening period:

A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL)

E. Adequate pulmonary function defined as:

no or mild dyspnea (≤ Grade 1)
oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.

Exclusion Criteria:

M3 marrow at the completion of 1st line induction therapy
M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening.
Philadelphia chromosome positive ALL
Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
Prior tyrosine kinase inhibitor therapy
Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy

Other protocol-defined inclusion/exclusion may apply.

Study Location

Novartis Investigative Site

Recruiting

Gent,9000,Belgium

Novartis Investigative Site

Recruiting

Montreal,Quebec,H3T 1C5,Canada

Novartis Investigative Site

Recruiting

Calgary,Alberta,T3B 6A8,Canada

Novartis Investigative Site

Recruiting

Monza,MB,20900,Italy

Novartis Investigative Site

Recruiting

Roma,RM,00165,Italy

Prinses Maxima Centrum voor Kinderoncologie

Recruiting

Utrecht,R. Pieters,3584 - CS,Netherlands

Novartis Investigative Site

Recruiting

Oslo,0424,Norway

Novartis Investigative Site

Recruiting

Esplugues De Llobregat,Barcelona,08950,Spain

Novartis Investigative Site

Recruiting

Goteborg,SE 416 85,Sweden

Novartis Investigative Site

Recruiting

Stockholm,141 86,Sweden

Novartis Investigative Site

Recruiting

London,WC1E 6HX,United Kingdom

Novartis Investigative Site

Recruiting

London,WC1N 3JH,United Kingdom

Childrens Hospital Los Angeles SC CTL019

Recruiting

Los Angeles,Lee Chen (323-361-8670) email: [email protected] -- Emily Hsieh,90027 - California,United States

Texas Children's Cancer and Hematology Center

Recruiting

Houston,Grace Anand (832-824-1000) email: [email protected] -- Rayne Rouce,77030 - Texas,United States

Monroe Carell Jr Childrens Hospital at Vanderbilt

Recruiting

Nashville,(615-321-5247) -- Carrie Kitko,37232 - Tennessee,United States

Oregon Health and Science University .

Recruiting

Portland,Nycole Ferguson (503-494-5893) email: [email protected] -- Bill Chang,97239-3098 - Oregon,United States

Duke University Medical Center .

Recruiting

Durham,Eileen Phifer (919-681-6898) email: [email protected] -- Timothy A Driscoll,27710 - North Carolina,United States

University of Minnesota CAEB071B2201

Recruiting

Minneapolis,Mollie Koppes (612-273-6212) email: [email protected] -- Peter Gordon,55455 - Minnesota,United States

The Childrens Hosp of Philadelphia Div Gastroint., Hepat. & Nutr.

Recruiting

Philadelphia,Aakruti Sharma (215-590-2985) email: [email protected] -- Shannon Maude,19104 - Pennsylvania,United States

Childrens Hospital of Orange County CHOC Children's

Recruiting

Orange,Tina Templeman email: [email protected] -- Van Huynh,92868-3874 - California,United States

Nationwide Childrens Hospital suite T6B

Recruiting

Columbus,Trittnee Robinson (614-722-2556) email: [email protected] -- Mark Ranalli,43205 - Ohio,United States

Phoenix Children's Hospital

Recruiting

Phoenix,Dresden Whitehead (602-546-0985) email: [email protected] -- Dana Salzberg,85016 - Arizona,United States

Ann and Robert H Lurie Childrens Hospital of Chicago .

Recruiting

Chicago,Eric Brown (312-227-4811) email: [email protected] -- Sonali Chaudhury,60611 - Illinois,United States

University of Utah Clinical Trials Office .

Recruiting

Salt Lake City,Keeley Best (801-587-5711) email: [email protected] -- Luke Maese,84108 - Utah,United States

James Whitcomb Riley Hospital for Children

Recruiting

Indianapolis,Jennifer Pencek (317-274-4281) email: [email protected] -- April Rahrig,46202 - Indiana,United States

UCSF Medical Center .

Recruiting

San Francisco,Emily Theobald (415-353-1351) email: [email protected] -- Michelle Hermiston,94143 - California,United States

Childrens Hospital of Wisconsin

Recruiting

Milwaukee,Tara Murphy email: [email protected] -- Julie-An Talano,53226 - Wisconsin,United States

Children s Hospital of Alabama

Recruiting

Birmingham,Colleen Quinn email: [email protected] -- Matthew Kutny,35233 - Alabama,United States

University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping Address

Recruiting

Madison,Jenny Weiland email: [email protected] -- Christian Capitini,53792 - Wisconsin,United States

Johns Hopkins All Childrens

Recruiting

Saint Petersburg,Joanna Gallacher email: [email protected] -- Deepakbabu Chellapandian,33701 - Florida,United States

Univ Hospital - Cleveland/Rainbow Babies and Children's Hosp Pediatric Nephrology

Recruiting

Cleveland,Jahnahn Taghiani (218-844-3681) email: [email protected] -- Duncan Stearns,44106 - Ohio,United States

Childrens National Hospital

Recruiting

Washington,(202-476-5000) -- Reuven Schore,20010 - District of Columbia,United States

Children's Healthcare of Atlanta Emory University IRB

Recruiting

Atlanta,Sarah Votaw email: [email protected] -- Muna Qayed,30342 - Georgia,United States

Rady Children s Hospital CTBM100C2401

Recruiting

San Diego,(858-966-8153) -- Deborah Schiff,92123 - California,United States

Washington Univ School of Medicine CTBM100C2412

Recruiting

Saint Louis,Bethany Kellogg (314-454-2253) email: [email protected] -- Thomas Pfeiffer,63110 - Missouri,United States

Mattel Childrens Hospital UCLA

Recruiting

Los Angeles,Eunice Kim email: [email protected] -- Satiro De Oliveira,90095 - California,United States

Univ of Texas Southwest Med Center

Recruiting

Dallas,Taryn Harris (214-648-1390) email: [email protected] -- Samuel John,75390-9034 - Texas,United States

Cinn Children Hosp Medical Center

Recruiting

Cincinnati,Adam Nelson (800-344-2462) email: [email protected] -- Christine Phillips,45229-3039 - Ohio,United States

Children's Hospital of Richmond at VCU Pediatric Hematology Oncology

Recruiting

Richmond,Grace Garren (804-828-9605) email: [email protected] -- Elizabeth Krieger,23219 - Virginia,United States

Roswell Park Cancer Institute Main Centre

Recruiting

Buffalo,(716-845-4485) -- Clare Twist,14263 - New York,United States

Yale School of Medicine

Recruiting

New Haven,Aron Flagg,06519 - Connecticut,United States

Medical Uni of South Carolina Medical Univ of SC

Recruiting

Charleston,Matt Smith (843-876-8614) email: [email protected] -- Michelle Hudspeth,29425 - South Carolina,United States

City of Hope National Medical

Recruiting

Duarte,(+16262564673#85013) -- Anna Pawlowska,91010 - California,United States

University of Chicago Hospital .

Recruiting

Chicago,James Labelle,60637 - Illinois,United States

Childrens Hospital Colorado .

Recruiting

Aurora,Darren Drake (720-777-5379) email: [email protected] -- Kelly Maloney,80045 - Colorado,United States

Stanford University Medical Center .

Recruiting

Stanford,Alexandria Lim (650-723-4000) email: [email protected] -- Kara Davis,94304 - California,United States

Methodist Children's Hospital .

Recruiting

San Antonio,Mark De Hoyos email: [email protected] -- Amanda Lipsitt,78229 - Texas,United States

Cleveland Clinic Foundation Main Centre

Recruiting

Cleveland,Nicole Previte (216-442-5232) email: [email protected] -- Rabi Hanna,44195 - Ohio,United States

University of Michigan

Recruiting

Ann Arbor,(734-936-8538),48109-2800 - Michigan,United States

Worldwide Contacts

If the location of your choosing does not feature any contact detail, please reach out using the information below.

Novartis Pharmaceuticals

Novartis Pharmaceuticals