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Clinical Trials/ISRCTN04804337
ISRCTN04804337CompletedPhase 1

Phase I dose-escalation study of oral administration of the selective Bcl2 inhibitor S55746 in patients with refractory or relapsed Chronic Lymphocytic Leukaemia and B-Cell Non-Hodgkin Lymphoma

Institut de Recherches Internationales Servier (France)0 sites120 target enrollmentStarted: March 21, 2014Last updated:
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Conditions

Trial Snapshot

Phase
Phase 1
Status
Completed
Sponsor
Enrollment
120
Study OverviewEligibility CriteriaInvestigatorsRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type
Interventional

Eligibility Criteria

Sex
All

Inclusion Criteria

  • •Current inclusion criteria:
  • •1. Women or men aged >/=18 years
  • •2. Patients with a measurable histologically confirmed FL, MCL, DLBCL, SLL and MZL (Arm A) or patients with an evaluable immunophenotypically confirmed CLL (Arm B), or patients with a measurable MM t(11;14) (arm A expansion part) according to IMWG criteria
  • •3. Previously treated relapsed after or refractory disease to standard treatments, and require treatment in the opinion of the investigator
  • •4. Estimated life expectancy > 12 weeks
  • •5. WHO performance status 0-2
  • •6. Adequate bone marrow, renal and hepatic functions
  • •7. No evidence or treatment for another malignancy within 2 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed
  • •Additional eligibility criteria for food interaction cohort:
  • •8. Patients with B¬cell NHL and defined as low risk of TLS according to published criteria (Cairo et al., 2010)
  • •9. Patients not having taken any treatment likely to have an impact on S55746 absorption (antacids, antisecretory including H2-receptor antagonists and proton pump inhibitors) within 7 days prior to first S55746 intake
  • •Previous inclusion criteria as of 13/01/2017:
  • •1. Women or men aged >/=18 years
  • •2. Patients with a measurable histologically confirmed FL, MCL, DLBCL, SLL and MZL (Arm A) or patients with an evaluable immunophenotypically confirmed CLL (Arm B), or patients with a measurable MM t(11;14) (arm A expansion part) according to IMWG criteria
  • •3. Previously treated relapsed after or refractory disease to standard treatments, and require treatment in the opinion of the investigator
  • •4. Estimated life expectancy > 12 weeks
  • •5. WHO performance status 0-2
  • •6. Adequate bone marrow, renal and hepatic functions, normal coagulation profile
  • •7. No evidence or treatment for another malignancy within 2 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed
  • •Additional eligibility criteria for food interaction cohort:
  • •8. Patients with B¬cell NHL and defined as low risk of TLS according to published criteria (Cairo et al., 2010)
  • •9. Patients not having taken any treatment likely to have an impact on S55746 absorption (antacids, antisecretory including H2-receptor antagonists and proton pump inhibitors) within 7 days prior to first S55746 intake
  • •Inclusion criteria from 07/09/2016 to 13/01/2017:
  • •1. Women or men aged >/=18 years
  • •2. Patients with a measurable histologically confirmed FL, MCL, DLBCL, SLL and MZL (Arm A) or patients with an evaluable immunophenotypically confirmed CLL (Arm B), or patients with a measurable MM t(11;14) (arm A expansion part)according to IMWG criteria
  • •3. Previously treated relapsed after or refractory disease to standard treatments, and require treatment in the opinion of the investigator
  • •4. Estimated life expectancy > 12 weeks
  • •5. WHO performance status 0-1
  • •6. Adequate bone marrow, renal and hepatic functions, normal coagulation profile

Exclusion Criteria

  • •Current inclusion criteria:
  • •1. Previous treatment with a BH3 mimetic
  • •2. Previous chemotherapy within 3 weeks before first intake
  • •3. Radioimmunotherapy, radiotherapy within 8 weeks before first intake
  • •4. Major surgery within 3 weeks before first day of study drug dosing
  • •5. Corticosteroids > 20 mg prednisone equivalent per day within 7 days before first intake
  • •6. Anticoagulant oral drugs, aspirin > 325 mg/day within 7 days prior to first S 55746 intake
  • •7. Positive direct antiglobulin test (Coombs test) and haptoglobin below normal value
  • •8. Prior allogenic stem cell transplant
  • •9. Autologous stem cell transplant within 3 months before the first intake of S55746.
  • •10. NHL patients diagnosed with Post¬Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukaemia
  • •11. Human immunodeficiency virus (HIV)
  • •12. Known acute or chronic hepatitis B or hepatitis C
  • •13. Impaired cardiac function
  • •14. Medications known to prolong QTc interval
  • •15. History or/ clinically suspicious for cancer-related CNS disease
  • •16. Solitary extramedullary plasmacytoma
  • •17. Strong or moderate CYP3A4 inhibitors/inducers (treatment, food or drink products)
  • •18. Treatment highly metabolized by the CYP3A4 or CYP2D6 and/or substrates with a narrow therapeutic index, multienzyme and/or OATP substrates and/or P-gp, or herbal products.
  • •19. Known hypersensitivity to rasburicase
  • •20. G6PD deficiency and other cellular metabolic disorders known to cause haemolytic anaemia
  • •21. Laboratory Signs of Tumor Lysis Syndrome
  • •22. Patients receiving proton pump inhibitor
  • •Previous exclusion criteria as of 13/01/2017:
  • •1. Previous treatment with a BH3 mimetic
  • •2. Previous chemotherapy within 3 weeks before first intake
  • •3. Radioimmunotherapy, radiotherapy within 8 weeks before first intake
  • •4. Major surgery within 3 weeks before first day of study drug dosing
  • •5. Corticosteroids > 20 mg prednisone equivalent per day within 7 days before first intake
  • •6. Anticoagulant oral drugs, aspirin > 325 mg/day
  • •7. Positive direct antiglobulin test (Coombs test) and haptoglobin below normal value
  • •8. Prior allogenic stem cell transplant
  • •9. Autologous stem cell transplant within 3 months before the first intake of S55746.
  • •10. NHL patients diagnosed with Post¬Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukaemia
  • •11. Human immunodeficiency virus (HIV)
  • •12. Known acute or chronic hepatitis B or hepatitis C
  • •13. Impaired cardiac function
  • •14. Medications known to prolong QTc interval
  • •15. History or/ clinically suspicious for cancer-related CNS disease
  • •16. Solitary extramedullary plasmacytoma
  • •17. Strong or moderate CYP3A4 inhibitors/inducers (treatment, food or drink products)
  • •18. Treatment highly metabolized by the CYP3A4 or CYP2D6 and/or substrates

Investigators

Sponsor
Institut de Recherches Internationales Servier (France)

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Phase I dose-escalation study of oral... | Clinical Trial