Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL and High Risk B-cell ALL at First Relapse. Determine Feasibility and Safety of CTL019 Therapy in Pediatric Patients With High Risk B-cell ALL That Relapsed < 6 Months Post All-HSCT. (ELIANA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02435849
Recruitment Status : Active, not recruiting
First Posted : May 6, 2015
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 16, 2015
First Posted Date  ICMJE May 6, 2015
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE April 8, 2015
Estimated Primary Completion Date November 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
Overall remission rate (ORR) = CR + CRi [ Time Frame: After manufactured pts have received CTL019 infuson and completed 3 months from study day 1 infusion or discontinued earlier ]
Efficacy of CTL019 therapy as measured by overall remission rate during the 3 months after CTL019 administration, which includes CR and CR with incomplete blood count recovery (CRi) as determined by IRC assessment.
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2015)
Overall remission rate (ORR) [ Time Frame: After 50 pts completed at least 6 months follow up ]
Efficacy of CTL019 therapy - ORR includes Complete Remission (CR) and CR with incomplete blood count recovery (CRi) as determined by independent review committee (IRC) assessment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Percentage of patients who achieve best overall response (BOR) or CR or CRi with an MRD negative bone marrow by central analysis using qPCR [ Time Frame: 3 months ]
  • Percentage of patients who achieve CR or CRi at month 6 without SCT between CTL019 infusion and Month 6 response assessment. [ Time Frame: 6 months ]
  • Duration of remission (DOR) [ Time Frame: 60 months ]
  • Percentage of patients who achieve CR or CRi with minimal residual disease negative bone marrow [ Time Frame: 3 months ]
  • Relapse-free survival [ Time Frame: 60 months ]
  • Event-free survival [ Time Frame: 60 months ]
  • Overall survival [ Time Frame: 60 months ]
  • Response at Day 28 +/- 4 days [ Time Frame: 1 month ]
  • Impact of baseline tumor burden on response [ Time Frame: 60 months ]
  • Percentage of patient who achieve CR or CRi and then proceed to SCT while in remission before Month 6 response assessment [ Time Frame: 6 months ]
  • Quality of response using MRD disease assessments before treatment at day 28 +/-4 days after treatment using central assessments by qPCR and before SCT by local assessment (flow or PCR) [ Time Frame: 60 months ]
  • Safety of CTL019 therapy [ Time Frame: 60 months ]
  • Characterize in vivo cellular PK profile of CTL019 cells in target tissues [ Time Frame: 60 months ]
  • Prevalence and incidence of immunogenicity to CTL019 [ Time Frame: 60 months ]
  • Effects of CTL019 therapy on Patient Reported Outcomes [ Time Frame: 60 months ]
  • Derivation of a score to predict cytokine release syndrome [ Time Frame: 3 months ]
  • Describe the profile of soluable immune factors that may be key to cytokine release syndrome [ Time Frame: 6 months ]
  • Describe levels of B and T cells (blood and bone marrow) prior to and following CTL019 infusion for safety monitoring [ Time Frame: 3 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2015)
  • Percentage of patients who achieve CR or CRi at Month 6 without SCT between CTL019 infusion and Month 6 response assessment [ Time Frame: 60 months ]
  • Percentage of patients who achieve CR or CRi and proceed to SCT while in remission before Month 6 response assessment [ Time Frame: 60 months ]
  • Duration of remission (DOR) [ Time Frame: 60 months ]
  • Percentage of patients who achieve CR or CRi with minimal residual disease negative bone marrow [ Time Frame: 60 months ]
  • Relapse-free survival [ Time Frame: 60 months ]
  • Event-free survival [ Time Frame: 60 months ]
  • Overall survival [ Time Frame: 60 months ]
  • In vivo cellular PK profile (levels, persistence, trafficking) of CTL019 cells [ Time Frame: 60 months ]
  • Prevalence/incidence of immunogenicity to CTL019 [ Time Frame: 60 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL and High Risk B-cell ALL at First Relapse. Determine Feasibility and Safety of CTL019 Therapy in Pediatric Patients With High Risk B-cell ALL That Relapsed < 6 Months Post All-HSCT.
Official Title  ICMJE A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell Acute Lymphoblastic Leukemia
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 and high risk B-cell ALL at first relapse. Determine feasibility and safety of CTL019 therapy in pediatric patients with high risk B-cell ALL that relapsed < 6 months post allo-HSCT.
Detailed Description

This is a three Cohort, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL (Main Cohort closed for an enrollment), high risk B-cell ALL patients at first relapse (Cohort 1 open for an enrollment), and feasibility and safety of CTL019 in high risk B-cell ALL patients that relapsed <6 months post allo-HSCT (Cohort 2 is open for an enrollment).

The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and Survival Follow-up. The total duration of the study is 5 years from CTL019 cell infusion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Group 1: pediatric patients with relapsed and refractory B-cell ALL (closed for an enrollment) Group 2: pediatric patients with high risk B-cell ALL at first relapse (open for an enrollment) Group 3: pediatric patients with high risk B-cell ALL that relapsed < 6 months post all-HSCT (open for an enrollment)
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoblastic Leukemia
  • Acute
  • High Risk
  • Childhood
Intervention  ICMJE Biological: Single dose of CTL019
2 to 5 x 10(6) autologous CTL019 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion.
Study Arms  ICMJE Experimental: Single dose of CTL019
2 to 5 x 10(6) autologous CTL019 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion.
Intervention: Biological: Single dose of CTL019
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 27, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: May 1, 2015)
67
Estimated Study Completion Date  ICMJE November 29, 2022
Estimated Primary Completion Date November 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Main Cohort closed for an enrollment):

  • Relapsed or refractory pediatric B-cell ALL

    1. 2nd or greater Bone Marrow (BM) relapse OR.
    2. Any BM relapse after allogeneic stem cell transplantation (SCT) and must be ≥ 6 months from SCT at the time of CTL019 infusion OR.
    3. 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.
    4. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated OR.
    5. Ineligible for allogeneic SCT.
  • For relapsed patients, documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry.
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
  • Life expectancy > 12 weeks.
  • Age 3 at the time of screening to age 21 at the time of initial diagnosis
  • Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.

Exclusion Criteria (Main Cohort closed for an enrollment):

  • 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 all women physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception from signing informed consent and through at least 12 months after the CTL019 infusion
  • Sexually active males must use a condom during intercourse from signing informed consent to at least 12 months after the CTL019 infusion

Inclusion Criteria (Cohort 1 open for an enrollment):

a. B-cell acute lymphoblastic leukemia and:

  • First relapse AND hypodiploid cytogenetics: fewer than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone 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)
  • For relapsed patients, documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry.
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
  • Life expectancy > 12 weeks.
  • Age up to 25 years at the time of screening.
  • Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.

Exclusion Criteria (Cohort 1 , open for an enrollment):

  • 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 of nursing (lactating) women.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception from signing informed consent and through at least 12 months after the CTL019 infusion
  • Sexually active males must use a condom during intercourse from signing informed consent to at least 12 months after the CTL019 infusion

Inclusion Criteria (Cohort 2 open for an enrollment):

a. B-cell acute lymphoblastic leukemia and:

  • Any BM relapse after allogeneic stem cell transplantation (allo-HSCT) and must be < 6 months from HSCT at the time of CTL019 infusion
  • For relapsed patients, documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry.
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
  • Life expectancy > 12 weeks.
  • Age up to 25 years at the time of screening.
  • Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.

Exclusion Criteria (Cohort 2 , open for an enrollment):

  • 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 all women physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception from signing informed consent and through at least 12 months after the CTL019 infusion
  • Sexually active males must use a condom during intercourse from signing informed consent to at least 12 months after the CTL019 infusion

Other protocol-defined inclusion/exclusion may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Italy,   Japan,   Norway,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02435849
Other Study ID Numbers  ICMJE CCTL019B2202
2013-003205-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP