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)

• Status: Completed
• Trial end date: 2007-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:

• Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797.

• Phase II: the recommended dose level of CHR-2797, as determined in phase I, will be administered to a further cohort of approximately 40 patients to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chroma Therapeutics
• Treatments: Glycine; Tosedostat

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.