A phase I/II clinical study of deliverability and efficacy of high dose lenalidomide for the treatment of adult patients with acute lymphoblastic leukaemia
A phase I/II clinical study of deliverability and efficacy of high dose lenalidomide for the treatment of adult patients with acute lymphoblastic leukaemia.
Dr Sushrut Patil
9 participants
Sep 15, 2013
Interventional
Conditions
Summary
The aim of this study is to assess the deliverability and efficacy of high dose lenalidomide for the treatment of adult patients with acute lymphoblastic leukaemia. Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with relapsed or refractory acute lymphoblastic leukaemia, which is unsuitable for further intensive chemotherapy. Study details All participants in this study will receive a drug called lenalidomide (Revlimid), which is administered as oral capsule. Treatment will be delivered in 28 days cycles until disease progression or unacceptable toxicity. The dose of lenalidomide administered will potentially be twice or thrice the dose that it is approved in Australia for the treatment of other blood cancers. Lenalidomide works against the cancer via multiple mechanisms. It damages the genetic code (DNA) of cancer cells (there is no evidence to suggest that normal cells are affected the same way), dampens the pro-survival genes in cancer cells and boosts the body’s natural immune response against the cancer cells. Lenalidomide has been found to be effective in cancers such as multiple myeloma, chronic lymphatic leukaemia, non Hodgkin’s lymphoma and acute myeloid leukaemia. However, it’s effectiveness is not examined exclusively in subjects with ALL. Participants will be regularly assessed throughout the duration of the trial in order to evaluate safety and efficacy of treatment.
Eligibility
Inclusion Criteria24
- ALL patients over the age 18 years with relapsed or refractory disease who are unsuitable for further intensive chemotherapy.
- Provision of written informed consent
- Life expectancy of greater than 3 months in relation to diseases other then ALL
- ECOG performance status 0 – 3
- Electrolyte levels (potassium, calcium (albumin-adjusted), magnesium, phosphorous) within normal limits (WNL) or easily correctable with supplements
- Adequate hepatic function as defined by bilirubin less than or equal to 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than of equal to 3 x ULN
- Adequate renal function, with serum creatinine equal to or less than 1.5 x ULN
- Patients with no uncontrolled active infection
- Women of childbearing potential (WCBP) must:
- a. Use two forms of contraception simultaneously
- b. Have a negative pregnancy test prior to start of study therapy.
- c. She must agree to ongoing pregnancy testing during the course of the study at specified intervals.
- d. This applies even if the subject practices complete and continued sexual abstinence
- Criteria for Women of non-childbearing potential:
- A female patient or a female partner of a male patient is considered to have childbearing potential if she is a sexually mature woman who:
- i)has not undergone a hysterectomy or bilateral oopherectomy
- ii) has not been naturally post menopausal for at least 24 consecutive months, i.e. has had menses at any time in the preceding 24 months. Note: amenorrhoea following cancer therapy does not rule out childbearing potential.
- Male subjects must:
- a. Agree to use a condom during sexual contact with a WCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and for 28 days after cessation of study therapy.
- b. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy
- All subjects must:
- a. Have an understanding that the study drug could have a potential teratogenic risk.
- b. Agree not to share study medication with another person.
- c. Agree not to donate blood during treatment with study therapy and for at least 28 days after cessation of study
Exclusion Criteria7
- Any serious medical or psychiatric conditions which the investigator feels may interfere with the patient’s ability to give informed consent or participate in the procedures or evaluations of the study
- History of major non-compliance to medication
- Evidence of only CNS leukemia in absence of systemic disease
- Uncontrolled viral infection with known HIV or Hepatitis type B or C
- Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that prevents the patient from absorbing or taking oral medication
- Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) that in the opinion of the investigator could potentiate unacceptable safety risks or jeopardise compliance with the protocol
- Female patients who are pregnant or breastfeeding and the lack of adequate contraception in females of childbearing potential, or their partners
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Interventions
This trial involves the use of the oral capsules lenalidomide. In the induction phase, patients will be treated with lenalidomide 50 mg/day for 28 days, followed 2 weeks later by another cycle at the same dose. In patients with progressive disease after or during first cycle or patients failing to reduce bone marrow blast count to less than 50% of diagnosis, further two cycles with 65mg (and 75 mg/day, if not responding to 65 mg/day) lenalidomide are planned. In patients with rapidly progressive disease, dexamethasone 20 mg/m2 may be administered weekly for 2 weeks, till the patient has received at least one cycle of 75 mg/day dose. Responding patients will receive 25 mg/day lenalidomide 21 days every month till disease progression as maintenance therapy. Patients experiencing serious toxicity or disease progression will be taken off study. For patients developing a toxicity which in investigator’s opinion doesn’t warrant discontinuation of lenalidomide, may be considered for dose de-escalation if the disease is not progressing. Objective evidence for biological activity of the strategy will be assessed using sensitive flow-based assays on bone marrow samples at baseline, at weeks 4 and 10 then 3 monthly of maintenance therapy. Lenalidomide will be supplied by the clinical trials pharmacy.Drug accountability and monitoring treatment adherence will be managed in part by the practise of returning containers and/or unused stock to the pharmacy. Regular hospital visits and blood test are also required. If a response rate of >20% obtained or no patient receives at least one cycle of 75 mg/day lenalidomide, to verify the safety and efficacy of the higher doses level, further patients will be enrolled to an expansion phase until a total of 14 patients have been recruited to the entire study. For patients relapsing after allogeneic HSCT, the following schedule will be followed: Lenalidomide will be dosed at 10mg daily for 21 of 28 days for cycle #1 (28 day cycle) and escalated to 15mg daily for 21 of 28 days for cycle #2 in the absence of treatment emergent aGvHD. Dexamethasone will be given for the first 2 cycles only, at a dose of 40mg weekly in cycle #1 and 20mg weekly in cycle #2. Dose modification will be allowed for lenalidomide (15mg -> 10mg-> 5mg) and dexamethasone (40mg -> 20mg -> 10mg) as per standard criteria. Dexamethasone will be given as an oral tablet. Study drugs must be ceased and recommencement is not permitted upon development of graft versus host disease. This safety study may form the basis of a larger phase 2 co-operative study to determine whether maintenance therapy with lenalidomide improves survival in ALL.
Locations(1)
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ACTRN12613000993796