This study is examining the safety and tolerability of a new drug (Everolimus) in combination with chemotherapy in the treatment of relapsed adult acute lymphobastic leukaemia
- Conditions
- acute lymphobastic leukaemia (ALL)Cancer - Leukaemia - Acute leukaemia
- Registration Number
- ACTRN12610000405011
- Lead Sponsor
- Australasian Leukaemia and Lymphoma Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 20
Morphologically and immunophenotypically confirmed diagnosis of precursor B ALL, negative for Philadelphia chromosome/ bcr-abl fusion transcripts, in first or subsequent relapse more than 6 months after starting treatment with a standard combination chemotherapy protocol.
Has provided written informed consent
Must be surgically sterile or female and postmenopausal (ie >12 mths since the last menstrual cycle) or, if capable of parenting a child, must be using medically acceptable and adequate method of contraception while undergoing protocol treatment and until 90 days after the last treatment.
Adequate renal, hepatic and cardiac functions at Screening as defined by:
Serum bilirubin <2.5 x upper limit of normal (ULN)
Serum creatinine < 1.5ULN, unless medically correctable
Adequate cardiac function with left ventricular ejection fraction (LVEF) >40% and no major left ventricular dysfunction
An Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less at Screening
Patients with other immunophenotypic variants of ALL (precursor T, mature B)
Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening.
Patients who have relapsed after an allogeneic transplant
Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any investigational agent within 4 weeks prior to commencing study treatment
Radiotherapy within 14 days of commencing study treatment.
Prior therapy with mammalian target of rapamycin (mTOR) inhibitors (sirolimus, temsirolimus, everolimus)
Uncontrolled diabetes mellitus
CYP3A4 enzyme inducing anti-convulsant medication (eg phenytoin, phenobarbital, or carbemazepine), rifampin and rifabutin, and St. John’s Wort less than or equal to 14 days prior to study treatment
Ketoconazole less than or equal to 7 days before study treatment (Note: interaction with topical ketoconazole cannot be excluded).
Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
Unresolved toxicities from prior systemic therapy or radiotherapy that, in the opinion of the investigator, does not qualify the patient for study treatment.
Patients with known interstitial lung disease or severely impaired lung function (spirometry and diffusional capacity lung carbon monoxide (DLCO) 50% or less of normal and oxygen saturation of 88% or less at rest on room air).
Patients who have a history of another primary malignant disease, apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse.
Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as common terminology criteria (CTC) grade 2)
Chronic treatment with immunosuppressives
Patients who, in the opinion of the Investigator, have any severe and/or uncontrolled medical conditions or infections that may compromise study data
Untreated or symptomatic Central Nervous System (CNS) leukaemia
Previous adverse reaction to trial drug(s)
Patients with a known history of Human Immunodeficiency Virus (HIV) seropositivity
Uncontrolled Hepatitis B or C infection. Patients positive for Hepatitis B Virus (HBV) (Hepatitis B surface antigen (HBs Ag) that is not due to vaccination, or HBV deoxyribonucleic acid (DNA)) should undergo prophylactic antiviral therapy for 2 weeks prior to the first dose of RAD001, and for 4 weeks following the last dose of RAD001.
Participation in other therapeutic studies in the last 30 days except for studies with a non-medical intervention. Documented evidence of receiving placebo will be required.
Unable to receive treatment at an affiliated Australasian Leukaemia and Lymphoma Group (ALLG) centre
Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or to complete the protocol
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the safety of RAD001 given in combination with the Hyper CVAD regimen in patients with relapsed ALL. The primary measure of safety will be the duration of myelosuppression, as measured by time to recovery to grade 2 neutropenia.[Daily evaluations from start of treatment until day 42 of each chemotherapy course]
- Secondary Outcome Measures
Name Time Method To document the duration of severe thrombocytopenia defined as platelets <50x10e9/L.[Daily evaluations from start of treatment until day 42 of each chemotherapy course];To document and review the incidence of Grade 3 and 4 non-hematological toxicities.[Daily until day 18 following last study treatment and again at day 42 after last study treatment];To provide estimates of the complete remission (CR) rate, duration of remission and leukemia-free survival (LFS) and overall survival (OS) in patients treated with this combination as assessed by medical investigations consistent with standard of care[3 years after patient was registered to trial]