E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma is a plasma cell malignancy that is characterized by accumulation of clonal plasma cells, mainly in the bone marrow, leading to clinical manifestations such as anemia, bone destruction, and renal insufficiency. Despite progress in our understanding of the disease and improvement in therapeutic options therapy remains palliative. Studies have shown improvement in mortality in the recent years, but the 5 and 10 year-estimated survival rate for myeloma patients remains rather low. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with previously treated progressing multiple myeloma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of the feasibility, safety and dose limiting toxicity (DLT) of Oncocort as a monotherapy in patients with multiple myeloma. |
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E.2.2 | Secondary objectives of the trial |
Response according to IMWG Criteria Best response (percentage change of myeloma related measures) d Quality of life assessments (NCCN distress- and pain levels) Determine pharmacokinetics (PK)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previously diagnosed symptomatic MM according to International Myeloma Working Group (IMWG) criteria a. Previously treated with at least two therapy lines including at least one proteasome-inhibitor and at least one immunomodulatory drug b. Relapse after or progressive disease under last therapy according to IMWG criteria. 2. At least 18 years old 3. Measurable disease (M-protein and/or free light chains) in serum and/or urine 4. Willing and able to comply the study protocol visits and assessments 5. Willing to use highly effective methods of birth control 6. Written informed consent prior to study participation
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E.4 | Principal exclusion criteria |
1. Types of Multiple Myeloma previously shown to be irresponsive to dexamethasone monotherapy during the last 6 months 2. Plasma cell leukemia 3. Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg], and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody [anti-HCV]), and / or a positive HIV antibody screen 4. Severe abnormal organ function or laboratory results at the time of the Screening Visit: WBC <3.0 g/L, ANC <1.5 G/L, PLT <50 G/L, Sodium <135 mmol/L or >150 mmol/L, potassium <3.5 mmol/L or >5.5 mmol/L, calcium <2.0 mmol/L or > 2.9mmol/L, phosphorus <0.8 mmol/L, total bilirubin >1.5x ULN, AP >2.5x ULN, gammaGT >3x ULN, ALT >3x ULN, CK >2.5x ULN, Creatinine >2x ULN, fasting glucose >250 mg/dL, albumin <3 g/dL, cholesterol >300 mg/dL 5. Treatment with oral or injectable (including intra-articular) corticosteroids (CS) within 4 weeks prior to Screening Visit. Inhaled and dermal corticosteroid formulations are allowed. 6. Subjects who have received a chemotherapeutic treatment cycle including dexamethasone within 4 weeks prior to the Screening Visit 7. Known sensitivity to any component of the study drug or previous hypersensitivity reaction or other clinically significant reaction to intravenous medications, biologic therapy or IV radiocontrast agents 8. Active infection requiring systemic treatment 9. Planned major surgery during the study period or had undergone major surgery within 30 days prior to the Screening visit. 10. Pregnancy or breastfeeding 11. Prior history of pulmonary embolism 12. Prior history of gastrointestinal hemorrhage 13. Prior history of a psychiatric disorder 14. Any clinically significant hepatic, renal, cardiac, pulmonary, gastrointestinal, metabolic or endocrine disturbances, other medical or psychiatric condition, or clinically relevant abnormal values on any investigation, in the opinion of the Investigator, that could make the subject unsuitable for the study, could compromise subject safety, limit the subject’s ability to complete the study, and/or compromise the objectives of the study, including severe neuropathies or other painful conditions that might interfere with pain evaluation 15. Participation in another clinical investigation less than 4 weeks prior to inclusion 16. The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication. 17. The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study18. The subject is unwilling or unable to follow the procedures outlined in the protocol 19. The subject is mentally or legally incapacitated 20. Persons who are in a relationship of dependence to the Investigator or the Sponsor
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose limiting toxicity (DLT) defined as any toxicity of grade 3 or higher according to CTCAE 4.03
laboratory results considered to be DLT: WBC <1.0 G/L, PLT <25 G/L, sodium <125 mmol/L or >155 mmol/L, potassium <2.5 mmol/L or >6.0 mmol/L, calcium <1.75 mmol/L or >3.4 mmol/L, phosphorus <0.6 mmol/L, total bilirubin >3.0x ULN, AP >5x ULN, gamma GT >5x ULN, ALT (SGPT) >5x ULN, CK >5x ULN, Creatinine >3x ULN or >3x baseline, fasting glucose >500 mg/dL, albumin <2 g/dL, cholesterol >400 mg/dL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Feasibility -> during the study periode Safety -> during the study periode Dose limiting toxicity -> during the study periode
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E.5.2 | Secondary end point(s) |
• Response according to IMWG Criteria • Best response (percentage change of myeloma related measures) • Quality of life assessments (NCCN distress- and pain levels) • Pharmacokinetics (PK)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Response according to IMWG Criteria -> 4 and 8 weeks after the first dose Best response -> during the study period Quality of life assessments -> during the study period Pharmacokinetics -> determine after the analysis of blood samples |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dosisfindungs-Studie |
Dose Escalating Study |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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Phase I: After each cohort of 3 patients, the Data Monitoring Committee (DMC) will review the safety data and determine if further dose escalation is appropriate. Phase IIa: DMC will review safety data quarterly. If 3 or more patients of the Phase IIa cohort experience grade 3 toxicity or higher, study accrual will be held pending data review by the internal DMC. After any death in either study phase, accrual will also be held pending data review by the DMC. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |