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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-004955-36-BE
• Date of registration: 30/03/2006
• Prospective Registration: Yes
• Primary sponsor: Chroma Therapeutics Ltd.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 26/04/2006
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004955-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, Germany, United Kingdom

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment refractory Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM)
MedDRA version: 9.1 Level: LLT Classification code 10000880 Term: Acute myeloid leukaemia
MedDRA version: 9.1 Level: LLT Classification code 10028535 Term: Myelodysplastic syndrome unclassifiable
MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

Intervention(s)

Product Name: CHR-2797
Product Code: CHR-2797
Pharmaceutical Form: Capsule, hard
CAS Number: 240489-34-3
Current Sponsor code: CHR-2797
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: CHR-2797
Product Code: CHR-2797
Pharmaceutical Form: Capsule, hard
CAS Number: 240489-34-3
Current Sponsor code: CHR-2797
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: CHR-2797
Product Code: CHR-2797
Pharmaceutical Form: Capsule, hard
CAS Number: 240489-34-3
Current Sponsor code: CHR-2797
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Secondary Objective: 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.

Main Objective: 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.

Primary 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.

Secondary ID(s)

2005-004955-36-GB

CHR-2797-002