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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 70

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 system and can cause myelosuppression. Consequently supportive should be given to ensure adequate values, according to local guidelines.
5.A bone marrow aspirate/ biopsy performed within four weeks prior to study entry.
6.Adequate bone marrow, hepatic and renal function including the following:
a.Patients with high blast counts can be included in the trial, if they 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.
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 with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of the trial. A woman with reproductive potential is defined as one who is biologically capable of becoming pregnant. Patients who are not surgically sterile or postmenopausal must agree to use a medically acceptable and highly effective method of birth control for the duration of the study and to continue after the end of CHR-2797 treatment for a further 3 months (female patients) or for a further 6 months (for male patients and their partners). A highly effective method of birth control is defined as any method that results in a low failure rate, including implants, injectables, some intra-uterine devices (IUD’s), sexual abstinence, and vasectomy/ sterilization. Sexually active males and females using oral contraceptive pills should also use barrier contraception. Although there is no reason to believe that the use of CHR-2797 has an effect on the pharmacokinetics of hormonal contraceptives, this has not yet been proven.
* 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 platelet count(s) less than 20,000.
9.Patients who have had a blood transfusion (platelet support or packed cells) within 7 days prior to study entry.
10.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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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