E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To determine the efficacy of targeted radiotherapy delivered by an Yttrium-90 (90Y)-radiolabelled murine anti-CD66 monoclonal antibody, given in addition to high dose melphalan (200 mg/m2) in terms of disease response (complete remission rate and change of serum free light chan level pre and post yttrium-90-radiolabelled anti-CD66) in patients undergoing haematopoietic stem cell transplantation (HSCT) for multiple myeloma. |
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E.2.2 | Secondary objectives of the trial |
1. Determine the toxicity profile of Yttrium90-radiolabelled anti-CD66 MAb in the context of autologous stem cell transplantation.
2. Determine the effect of targeted radiotherapy on parameters of disease reponse, eg proportion of patients with partial remission, stable disease, progressive disease, remission duration (time to disease progression) and overall survival.
3. Determine the effect of targeted radiotherapy on engraftment when used in conjunction with high dose melphalan in patients undergoing autologous peripheral blood stem cell transplantation as treatment for multiple myeloma.
4. Investigate the pharmacokinetic (PK) behaviour of Indium-111 (111In) radiolabelled anti-CD66 MAb in man.
5. Continue to develop a dosimetry model based on SPECT and whole body gamma camera imaging following administration of the radiolabelled anti-CD66 Mab (at the Southampton site only).
6. Assess the proportion of patients that form human anti-murine antibodies (HAMA)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically or cytologically proven multiple myeloma.
• In PR after chemotherapy and before priming therapy for stem cell mobilization.
• Age greater than 18 years.
• Life expectancy of at least 24 weeks.
• World Health Organisation (WHO) performance status of < 2 (Appendix 1).
• Haematological and biochemical indices (These measurements must be performed within one week prior to the patient going on study.)
- Haemoglobin (Hb) ≥ 9.0 g/dl
- neutrophils ≥ 1.5 x 109/L
- platelets (Plts) ≥ 50 x 109/L
• Any of the following abnormal baseline liver function tests :
- Serum bilirubin ≤ 1.5 x upper normal limit
- Alanine amino-transferase (ALT)
- and/or aspartate amino-transferase (AST) ≤ 2.5 x upper limit of normal (ULN) unless due to tumour in which case up to 5 x ULN is permissible
• The following abnormal baseline renal function test:
- calculated creatinine clearance ≥ 50 ml/min (uncorrected value)
- or isotope clearance measurement ≥ 50ml/min
• No concurrent or recent (within 4 weeks) chemotherapy for the underlying haematological condition (excluding cyclophosphamide priming for stem cell harvest). This does not include thalidomide which is permitted.
• Although the BM remission status is not important, patients must have cellularity > 20%.
• Patients must have sufficient stem cells in cryo-storage for two transplant procedures, this is in case graft failure occurs as a result of therapy.
• Patients must be negative for human anti-mouse antibodies (HAMA). |
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E.4 | Principal exclusion criteria |
• Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosureas and Mitomycin-C) prior to treatment.
• All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities which in the opinion of the Investigator and LRF should not exclude the patient.
• Patients with BM cellularity < 20%.
• Patients who test positive for HAMA.
• Previous high dose therapy and autologous stem cell transplant.
• Patients in CR after chemotherapy and prior to APBSCT.
• Pregnant and lactating women are excluded.
• Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered.
• Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection.
• Patients with any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
• Patients known to be serologically positive for Hepatitis B, C or HIV.
• History of Allergy. In particular a history of allergy to rodents or rodent proteins.
• History of eczema, asthma.
• Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease (refer to Appendix 5)
• Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health.
Less than 4 x 106 CD34 positive cells per kg body weight.
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E.5 End points |
E.5.1 | Primary end point(s) |
Remission status pre and post transplantation, as defined for multiple myeloma by the European Blood and Marrow Transplantation Organisation (51). Specifically the number of patients in each arm achieving CR as defined in the EBMT response criteria. |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
High dose Melphalan alone |
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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 | 4 |
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 | 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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The entire trial will be stopped when:
• The targeted radiotherapy is considered too toxic to continue treatment prior to the required number of patients being recruited
• The stated number of patients to be recruited is reached.
• If after an interim analysis there is a statistically significant difference between the two arms of the study.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |