Phase I dose-escalation study of oral administration of S55746 in patients with B-Cell Non-Hodgkin Lymphoma
- Conditions
- Chronic Lymphocytic Leukaemia (CLL) and B-Cell Non-Hodgkin Lymphoma (NHL) including Follicular Lymphoma (FL) , Mantle Cell Lymphoma (MCL), Diffuse Large B-Cell Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma and and Multiple myeloma (MM)CancerChronic Lymphocytic Leukaemia (CLL) and B-Cell Non-Hodgkin Lymphoma (NHL) including Follicular Lymphoma (FL) , Mantle Cell Lymphoma (MCL), Diffuse Large B-Cell Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Multiple myeloma (MM)
- Registration Number
- ISRCTN04804337
- Lead Sponsor
- Institut de Recherches Internationales Servier (France)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 120
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Current primary outcome measures as of 13/01/2017:<br> 1. Dose Limiting Toxicities (DLTs) in cycle 1<br> 2. Maximum Tolerated Dose, defined as the highest drug dosage that is unlikely (<25% posterior probability) to cause DLTs in more than 33% of the treated patients in the first cycle of S 055746 treatment<br> 3. Safety profile at each visit, assessed by adverse events monitoring, laboratory tests, vital signs and performance status, clinical examination and ECG parameters<br><br> Previous primary outcome measures:<br> 1. Maximum Tolerated Dose will be evaluated following Dose Limiting Toxicities at the end of cycle 1 for a given dose measured by adverse events monitoring<br> 2. Safety profile at each visit measured by adverse events monitoring, ECG, cardiac function parameters, physical examination, performance status, vital signs and laboratory tests<br>
- Secondary Outcome Measures
Name Time Method