Phase III B in Acute Lymphoblastic Leukemia

NCT03123939 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CCTL019B2001X2016-001991-31
• Study Type: interventional
• Target: 69
• Locations: 9 countries
• Sites: 11

Brief Summary

This is a single arm, open-label, multi-center, phase III B study to determine the safety and efficacy of CTL019 in pediatric/young adult patients with r/r B-cell Acute Lymphoblastic Leukemia (ALL).

Conditions

Acute Lymphoblastic Leukemia

Keywords

ALL; Acute Lymphoblastic Leukemia; CTL019; relapsed/refractory pediatric/young adult

Outcome Measures

Primary Outcomes (1)

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

  Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months

  From CTL019 infusion until end of study, up to 12 months

Secondary Outcomes (22)

• Overall Remission Rate (ORR)

  From CTL019 infusion until Month 6

• Number of Participants Who Achieved CR or CRi at Month 6 Without Stem Cell Transplantation (SCT)

  Month 6

• Number of Participants Who Achieved CR or CRi and Then Proceeded to Stem Cell Transplantation (SCT) While in Remission Before Month 6 Assessment

  From CTL019 infusion until Month 6

• Duration of Response (DOR)

  Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)

• Relapse-free Survival (RFS)

  Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion)

Study Arms (1)

CTL019

EXPERIMENTAL

CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10\^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg)

Biological: CTL019

Interventions

CTL019 BIOLOGICAL

CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10\^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10\^8 CTL019 transduced viable T cells (for patients \> 50 kg)

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 B-cell ALL in pediatric or young adult patients:
• Second or greater bone marrow relapse.
• Any bone marrow relapse after allogeneic SCT and must be ≥ 4 months from SCT at the time of CTL019 infusion OR
• Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia OR
• Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
• Ineligible for allogeneic SCT
• For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of program entry.For relapsed or refractory patients previously treated with blinatumomab, CD19 tumor expression must be demonstrated (via flow cytometry) at Screening.
• Adequate organ function defined as:
• A serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL). Age Male Female: to \< 2 years 0.6 0.6; to \< 6 years 0.8 0.8; 6 to \< 10 years 1.0 1.0; 10 to \< 13 years 1.2 1.2; 13 to \< 16 years 1.5 1.4; ≥ 16 years 1.7 1.4.
• ALT ≤ 5 times the upper limit of normal (ULN) for age.
• Bilirubin \< 2.0 mg/dL.
• Minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation \> 91% on room air.
• Left Ventricular Shortening Fraction ≥ 28% by echocardiogram, or Left Ventricular Ejection Fraction ≥ 45% by echocardiogram or Multiple Uptake Gated Acquisition (MUGA).
• Life expectancy \> 12 weeks.
• Age less than 26 at the time of screening.

You may not qualify if:

• Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell surface immunoglobulin (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.
• Prior treatment with any gene therapy product. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab 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 GVHD. Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening Investigational medicinal product within the last 30 days prior to screening. Pregnant or nursing women.Women of child-bearing potential and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CTL019 infusion.
• The following medications are excluded:
• Steroids: Therapeutic systemic doses of steroids must be stopped \> 72 hours prior to CTL019 infusion.
• Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed \> 6 weeks prior to CTL019 infusion.
• GVHD therapies: Any systemic drug used for GVHD must be stopped \> 4 weeks prior to CTL019 infusion to confirm that GVHD recurrence is not observed.
• Chemotherapy:
• TKIs and hydroxyurea must be stopped \> 72 hours prior to CTL019 infusion.
• must be stopped \> 1 week prior to CTL019 infusion: vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate \< 25 mg/m2, cytosine arabinoside \< 100 mg/m2/day, asparaginase (non pegylated).
• must be stopped \> 2 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside \> 100 mg/m2, anthracyclines, cyclophosphamide, methotrexate ≥ 25 mg/m2).
• Pegylated-asparaginase must be stopped \> 4 weeks prior to CTL019 infusion.
• CNS disease prophylaxis: CNS prophylaxis treatment must be stopped \> 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate).
• Radiotherapy
• Non-CNS site of radiation must be completed \> 2 weeks prior to CTL019 infusion.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

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, 75019, France

Location

Novartis Investigative Site

Paris, 75475, 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 (1)

• 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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

tisagenlecleucel

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 21, 2017
• Study Start: April 24, 2017
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: July 21, 2021
• Results First Posted: July 21, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

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