Clinical trial NCT00689000 (phase 1/phase 2, status: completed)
Conditions: acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma
ICD codes: C92.A1, C92.A2, C92.61, C92.62, C92.A0, C92.60, D46.9, D46.C, D46.Z, C90.01, C90.02, C90.00
Drugs: chr-2797 (tosedostat): aminopeptidase inhibitor
SMILES: CC(C)C[C@H]([C@H](O)C(=O)NO)C(=O)N[C@H](C(=O)OC1CCCC1)C1=CC=CC=C1
Eligibility criteria:

        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.