Clinical Trial Page

Summary
EudraCT Number:2005-004955-36
Sponsor's Protocol Code Number:CHR-2797-002
National Competent Authority:Belgium - FPS Health-DGM
Clinical Trial Type:EEA CTA
Trial Status:Completed
Date on which this record was first entered in the EudraCT database:2006-03-30
Trial results
A. Protocol Information
A.1Member State ConcernedBelgium - FPS Health-DGM
A.2EudraCT number2005-004955-36
A.3Full title of the trial
A Phase I-II Study to Evaluate the Safety, Tolerability and Anti-Disease Activity of the Aminopeptidase Inhibitor, CHR-2797, in Elderly and/or Treatment Refractory Patients with Acute Myeloid Leukaemia or Multiple Myeloma
A.4.1Sponsor's protocol code numberCHR-2797-002
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorChroma Therapeutics Ltd.
B.1.3.4CountryUnited Kingdom
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCHR-2797
D.3.2Product code CHR-2797
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1CAS number 240489-34-3
D.3.9.2Current sponsor codeCHR-2797
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Information not present in EudraCT
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCHR-2797
D.3.2Product code CHR-2797
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1CAS number 240489-34-3
D.3.9.2Current sponsor codeCHR-2797
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number20
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Information not present in EudraCT
D.IMP: 3
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCHR-2797
D.3.2Product code CHR-2797
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1CAS number 240489-34-3
D.3.9.2Current sponsor codeCHR-2797
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number40
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Information not present in EudraCT
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Treatment refractory Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM)
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 9.1
E.1.2Level LLT
E.1.2Classification code 10000880
E.1.2Term Acute myeloid leukaemia
E.1.2 Medical condition or disease under investigation
E.1.2Version 9.1
E.1.2Level LLT
E.1.2Classification code 10028535
E.1.2Term Myelodysplastic syndrome unclassifiable
E.1.2 Medical condition or disease under investigation
E.1.2Version 9.1
E.1.2Level LLT
E.1.2Classification code 10028228
E.1.2Term Multiple myeloma
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
Primary objective(s):
•(Phase I) To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily, to elderly patients and patients with treatment refractory Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM).
•(Phase II) To evaluate the anti-leukaemia/myeloma effect of the recommended dose of single agent CHR-2797 (as determined in Phase I) in elderly and/or treatment refractory patients with AML, MDS or Multiple Myeloma.
E.2.2Secondary objectives of the trial
Secondary objectives :
•(Phase I and II) To determine trough levels of CHR-2797 and CHR-79888 when administered orally at different dose levels.
•(Phase II) To evaluate the safety and tolerability of the recommended dose of CHR-2797 when administered orally for up to 84 days to patients with a haematological malignancy.
•(Phase I and II) To obtain preliminary information on the safety and tolerability of CHR-2797 in patients who receive CHR-2797 in combination with adjunctive disease modifying therapy.

E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1.Signed, informed consent.
2.Patients with AML, MDS (subtype RAEB-1 or RAEB-2), or MM whose disease has relapsed or is refractory to front line and/ or salvage therapy; elderly patients (≥ 60 years) with AML, MDS, MM who are not candidates for chemotherapy and for whom other therapy is inappropriate*.
3.Patients should have recovered from the acute adverse effects of prior therapies (excluding alopecia and grade II neuropathy).
4.AML, MDS and MM are diseases of the haematopoetic and can cause myelosuppression; consequently supportive therapy should be given to ensure adequate values, according to local guidelines.
5.A bone marrow biopsy performed within four weeks prior to study entry.
6.Adequate bone marrow, hepatic and renal function including the following:
a.High blast counts are not an exclusion criteria and can be controlled by the use of hydroxyurea (500-3000 mg daily).
b.Total bilirubin ≤ 1.5 x upper normal limit.
c.AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit (or 5 x ULN in the presence of liver metastases).
d.Creatinine ≤1.5 x upper normal limit.
7.Age ≥ 18 years
8.Performance status (PS) ≤ 2 (ECOG scale).
9.Estimated life-expectancy greater than 3 months.
10.Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).
* There will be a clinical conference after completion of phase I to decide on patient population for phase II: AML/MDS or MM or both.
E.4Principal exclusion criteria
1.Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry- except for hydroxyurea (maximum daily dose is 3 g).
2.Indolent, smouldering myeloma, monoclonal gammopathy with unknown
significance.
3.Patients who need a daily dose of hydroxyurea greater than 3 g to control leukocytosis.
4.Co-existing active infection or serious concurrent illness.
5.Any co-existing medical condition that in the investigator’s judgement will
substantially increase the risk associated with the patient’s participation in the study.
6.Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
7.Gastrointestinal disorders that may interfere with absorption of the study drug.
8.Patients with platetlet count(s) < 20x10^9/L
9.Persistent grade II or greater toxicity from any cause (except haematological toxicities and peripheral neuropathy).
11.Patients with grade III–IV peripheral neuropathy.
12.Pregnant or breast-feeding women.
E.5 End points
E.5.1Primary end point(s)
Primary end point in Phase I: Dose Limiting Toxicity (DLT). DLT has been defined as any of the following events that is determined by the investigator to be possibly or probably related to CHR-2797 and that occurred during the first 28 days of treatment in Phase I, irrespective of whether the toxicity resolved:
•Drug-related non-haematological grade III/IV toxicity, with the exceptions of fatigue, nausea and vomiting, diarrhoea, alopecia, myalgia or arthralgia unless appropriate prophylactic or therapeutic measures have been administered.
•Grade IV thrombocytopenia, defined as a reduction in platelet count of > 75%, compared to baseline.
•Grade IV anaemia, defined as a reduction in haemoglobin of > 75%, compared to pre-treatment.
•Inability to tolerate 28 days of therapy due to toxicity.

Primary end point in Phase II: Biological activity as determined by meaningful tumour response (defined as Complete Response, Partial Response, Haematological Improvement or Minimal Response). Stable disease is defined as either Stable Disease or No Change.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) Yes
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other Yes
E.7.1.3.1Other trial type description
phase I-II study
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Information not present in EudraCT
E.8.2.2Placebo Information not present in EudraCT
E.8.2.3Other 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.8.4.1Number of sites anticipated in Member State concerned5
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA3
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.7Trial 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
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months9
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months9
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) Yes
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state20
F.4.2 For a multinational trial
F.4.2.1In the EEA 70
F.4.2.2In the whole clinical trial 70
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Details provided in the protocol
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2006-04-06
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2006-04-26
P. End of Trial
P.End of Trial StatusCompleted
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