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PK, PD, Safety and Immunogenicity of Spectrila in Adults With Acute B-cell Lymphoblastic Leukaemia

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03156790
Recruitment Status : Recruiting
First Posted : May 17, 2017
Last Update Posted : August 24, 2020
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
medac GmbH

Brief Summary:
This is a non-controlled, single-arm, open-label clinical trial to describe the PK, PD, immunogenicity and safety of ASNase. All subjects enrolled will receive the IP recombinant ASNase (Spectrila®). Since Spectrila is already approved in the European Economic Area for first-line treatment of ALL patients of all age groups and showed similar efficacy and safety in comparison to Asparaginase medac no blinding or control groups are necessary. As underlying treatment protocol the BRALL 2014 treatment protocol will be used.

Condition or disease Intervention/treatment Phase
Acute B-Cell Lymphoblastic Leukaemia Drug: Spectrila® Phase 2

Detailed Description:

The BRALL (Brazilian Acute Lymphocytic Leukaemia) treatment protocol was developed to standardise adult ALL treatment in Brazil since previously each centre used a different protocol. As in other treatment regimens of study groups, ASNase is an important component of ALL therapy. The rationale of the BRALL protocol was to use less myelotoxic drugs as daunorubicin, etoposide and cyclophosphamide and focus on more specific ALL directed therapies as asparaginase and methotrexate. The higher asparaginase dose regimen was chosen in BRALL 2014 to strengthen ASNase as major component of the treatment protocol while etoposide administration is reduced. Native ASNase is widely used and the data investigating non-inferiority, safety and tolerability of Asparaginase medac vs. Spectrila received a positive opinion from the European Medicines Agency (EMA). Nevertheless, data on efficacy and safety of Spectrila in adults are limited. Therefore, robust data on PK, pharmacodynamics (PD), safety and immunogenicity of Spectrila will be investigated in this trial in subjects with de novo ALL. The measurement of ASNase activity is considered to correlate with clinical effectiveness and therefore chosen as primary objective.

Subjects eligible for participation in this clinical trial will be treated with 3 intravenous doses of Spectrila of 10 000 U/m² BSA each during induction phase I of the underlying BRALL 2014 treatment protocol. Spectrila will be administered on Days 21, 23 and 25. Additionally, the subjects (standard risk subjects only) will receive doses of 10 000 U/m² BSA Spectrila each on Days 2, 4, 6, 9, 11 and 13 of the consolidation phase II, III and VI of BRALL 2014 treatment protocol. One final Analysis is planned.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Phase II Trial to Describe Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of Spectrila® With the Pharmaceutical Active Ingredient Recombinant L Asparaginase in Adult Subjects With Newly Diagnosed Acute B-Cell Lymphoblastic Leukaemia
Actual Study Start Date : April 26, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : April 2023


Arm Intervention/treatment
Experimental: Spectrila®
recombinant L-Asparaginase
Drug: Spectrila®
3 intravenous doses of 10 000 U/m² BSA each during induction phase I of the underlying BRALL 2014 treatment protocol on Days 21, 23 and 25. Additionally, the subjects (standard risk subjects only) will receive doses of 10 000 U/m² BSA each on Days 2, 4, 6, 9, 11 and 13 of the consolidation phase II, III and VI of BRALL 2014 treatment protocol.
Other Name: recombinant L-Asparaginase




Primary Outcome Measures :
  1. Asparaginase (ASNase) activity trough levels [ Time Frame: Day 21 until Day 31 ]
    Assessment of induction phase response, defined as subjects with asparaginase (ASNase) activity trough levels in serum ≥ 100 U/L in induction phase



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with newly diagnosed pathologically confirmed acute B-cell lymphoblastic leukaemia
  2. Female or male subjects between 18 and 55 years of age (inclusive)
  3. Subjects eligible for treatment and treated according to the underlying treatment protocol BRALL 2014
  4. Written informed consent given freely after the nature of the trial and disclosure of data has been explained to the subject
  5. The subject shows no evidence of a current infection with SARS-CoV-2 (as diagnosed by thorax tomography or PCR test or test for anti-SARS-CoV-2 antibodies).
  6. The subject expresses his/her understanding of the trial procedures and willingness to abide by them during the course of the trial
  7. Female subjects of child-bearing potential must use a highly effective method of contraception (pearl index less than 1%) such as complete sexual abstinence, combined oral contraceptive, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap/diaphragm with spermicide during the trial and for at least 3 months after Spectrila discontinuation.
  8. Men should use effective contraceptive measures and be advised to not father a child while receiving ASNase. As a precautionary measure it is recommended to wait at least for 3 months after completion of treatment.

Exclusion Criteria:

  1. Pre-treatment with any ASNase preparation
  2. Hypersensitivity to the active substance, Escherichia coli- ASNase preparation or to any of the excipients
  3. Pancreatitis at the time of treatment initiation or history of pancreatitis
  4. Pre-existing known coagulopathy
  5. Severe liver function impairment (bilirubin > three times the upper limit of normal [ULN]; transaminases > ten times ULN)
  6. History of serious haemorrhage or serious thrombosis
  7. Other current malignancies
  8. Uncontrolled active infection
  9. Evidence of infection with the human immunodeficiency virus, hepatitis B or C, human T-lymphotropic virus type I and II, syphilis or Chagas disease (American trypanosomiasis)
  10. Pregnancy as verified by a positive pregnancy test or nursing woman
  11. Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely
  12. Evidence or suspicion that the subject might not comply with the requirements of the trial protocol.
  13. Evidence or suspicion that the subject is unwilling or unable to understand the information given to him/her within the informed consent procedure
  14. Any other factor which in the investigator's opinion is likely to compromise the subject's ability to participate in the trial
  15. The subject is an employee or direct relative of an employee of the contract research organisation (CRO) involved in the trial, the trial site or medac.
  16. The subject is imprisoned or is lawfully kept in an institution.
  17. The subject has participated within 3 months before screening or plans to participate in a clinical trial (except the underlying treatment protocol BRALL 2014).
  18. Previous participation in this clinical trial -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03156790


Contacts
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Contact: Belinda Simoes, MD 55 16 36022663 bpsimoes@fmrp.usp.br

Locations
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Brazil
Universidade Estadual de Campinas Recruiting
Campinas, Brazil, 13083-878
Hospital das Clínicas da UFG Not yet recruiting
Goiânia, Brazil, 74605-020
Hospital de Clínicas Porto Alegre Not yet recruiting
Pôrto Alegre, Brazil, 90035-903
INCA Instituto Nacional do Cancer Not yet recruiting
Rio de Janeiro, Brazil, 20231-091
Hospital Estadual Mario Covas Recruiting
Santo André, Brazil, 09190 615
Hospital de Base de Sáo José Not yet recruiting
São José, Brazil, 15090-000
Hospital das Clínicas São Paulo USP Recruiting
São Paulo, Brazil, 05403-000
Sponsors and Collaborators
medac GmbH
Syneos Health
Investigators
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Principal Investigator: Belinda Simoes, MD Ribeirão Medical School Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto
Additional Information:
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Responsible Party: medac GmbH
ClinicalTrials.gov Identifier: NCT03156790    
Other Study ID Numbers: MC-Spectrila.1/ALL
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: August 24, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by medac GmbH:
recombinant L-Asparaginase
Spectrila®
Lymphoblastic Leukaemia
BRALL 2014
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Asparaginase
Antineoplastic Agents