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
Conditions
Interventions
Product Name: CHR-2797
Product Code: CHR-2797
Pharmaceutical Form: Capsule, hard
CAS Number: 240489-34-3
Current Sponsor code: CHR-2797
Sponsors
Chroma Therapeutics Ltd.
Eligibility
Sex/Gender
All
Inclusion 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ; 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. ; 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 reductio | — |
Countries
Belgium, Germany, United Kingdom
Outcome results
None listed