Safety and Anti-Disease Activity of CHR-2797 (Tosedostat) in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM)

Inclusion Criteria:

* Signed, informed consent.
* 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.
* Patients should have recovered from the acute adverse effects of prior therapies (excluding alopecia and grade II neuropathy).
* AML, MDS and MM are diseases of the haematopoietic system and can cause myelosuppression. Consequently supportive therapy should be given to ensure adequate values, according to local guidelines.
* A bone marrow aspirate/ biopsy performed within four weeks prior to study entry.
* Adequate bone marrow, hepatic and renal function including the following:

  1. 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).
  2. Total bilirubin ≤ 1.5 x upper normal limit.
  3. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit.
  4. Creatinine ≤1.5 x upper normal limit.
* Age ≥ 18 years
* Performance status (PS) ≤ 2 (ECOG scale).
* Estimated life-expectancy greater than 3 months.
* Female patients 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.

Exclusion Criteria:

* 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).
* Indolent, smouldering myeloma, monoclonal gammopathy with unknown significance.
* Patients who need a daily dose of hydroxyurea greater than 3 g to control leukocytosis.
* Co-existing active infection or serious concurrent illness.
* 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
* Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
* Gastrointestinal disorders that may interfere with absorption of the study drug.
* Patients with platelet count(s) \< 20,000.
* Patients who have had a blood transfusion (platelet support or packed cells) within 7 days prior to study entry.
* Persistent grade II or greater toxicity from any cause (except haematological toxicities and peripheral neuropathy).
* Patients with grade III-IV peripheral neuropathy.
* Pregnant or breast-feeding women.