E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory diffuse large B-cell lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the efficacy of GCS-100 with rituximab, ifosfomide, mesna, carboplatin, and etoposide (R-ICE) chemotherapy in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). |
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E.2.2 | Secondary objectives of the trial |
Determine the safety of GCS-100 in conjunction with cytotoxic chemotherapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is capable of understanding the purpose and risks of the study and is able to provide written Informed Consent.
2. Subject is male or female, aged at least 18 years.
3. Subject has histologically confirmed DLBCL, bi-dimensionally measurable by CT scan, with at least 1 lesion ≥1.5 cm in the greatest diameter. CT scan results must be available prior to dosing to establish eligibility.
4. Subject has relapsed or relapsed/refractory disease following at least 2 cycles of R-ICE chemotherapy as salvage chemotherapy, without PR or CR.
5. Subject has ≥4 weeks elapsed between last chemotherapy or immunotherapy exposure.
6. Subject has Eastern Collaborative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
7. Subject’s clinical laboratory values met all of the following criteria within the 14 days prior to Study Day 1, Cycle 1: a) Hemoglobin ≥9 g/dL b) Absolute neutrophil count >1.0 x 109/L without growth factor support. (ie, no prior myeloid colony stimulating factor use within 4 weeks prior to blood draw for screening absolute neutrophil count) c) Platelets ≥75 x 109/L d) Total bilirubin ≤2.0 X Institutional Upper Limit of Normal (IULN) e) Aspartate aminotransferase/alanine aminotransferase <2.5 X IULN, or <5X IULN in subjects with liver involvement of DLBCL f) Creatinine clearance >60 mL/min/1.73 m2 g) Serum sodium >130 mmol/L
8. Subject’s life expectancy is anticipated to be at least 3 months.
9. Female subjects of childbearing potential (ie, women who have not been surgically sterilized or have not been post-menopausal for at least 1 year) and male subjects with partners of childbearing potential must agree to use medically acceptable methods of contraception throughout the study period.
10. Subject is willing and able to comply with the prescribed treatment protocol and evaluations. |
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E.4 | Principal exclusion criteria |
1. Subject has received salvage with R-ICE in whom starting doses of any of the agents were administered at below 75% of the standard dosages defined in this study.
2. Subject has received high-dose chemotherapy with hematopoietic stem cell support or allogeneic stem cell transplantation (SCT).
3. Subject has rapidly progressive lymphoma or lymphoma threatening organ function.
4. Subjects with primary or secondary central nervous system lymphoma.
5. Subjects who have had treatment with an experimental (unlicensed) drug within 3 weeks prior to treatment with GCS 100.
6. Subject has not recovered from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy.
7. Subject has a known history of human immunodeficiency virus-related lymphoma, active hepatitis C, active hepatitis B, or prior history of infection with hepatitis B (HBcAb positive)
8. Subject has a clinically relevant active infection and/or a serious co-morbid medical condition such as recent myocardial infarction (within the last 6 months and no electrocardiographic evidence of acute ischemia or new conduction system abnormalities), unstable angina, difficult-to-control congestive heart failure, uncontrolled hypertension, difficult-to-control cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, and/or cirrhosis.
9. Subject had major surgery within 4 weeks prior to Study Day 1.
10. If female, subject is pregnant or breastfeeding.
11. Subject has a concomitant disease or condition, including laboratory abnormalities, which in the opinion of the Investigator could interfere with the conduct of the study or could put the subject at unacceptable risk. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome is overall response, defined as the sum of the Complet Response (CR) and and Partial Response (PR) rates. Response will be determined according to the International Harmonization Project guidelines. Response rate will be calculated along with a 95% confidence interval using the method of Chang to account for the 2-stage nature of the design. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |