The effect of the antiviral drug, Peg-interferon, in patients with relapsed haematological malignancy after initial sibling or volunteer unrelated allogeneic haematopoietic progenitor cell transplantation (HPCT)
A phase I / II study to evaluate the effect of pegylated-Interferon-2alpha on overall survival in patients with relapsed haematological malignancy after allogeneic haematopoietic progenitor cell transplantation (HPCT)
Royal Brisbane and Womens Hospital
30 participants
Jul 4, 2012
Interventional
Conditions
Summary
There are no standard approaches to treat haematological malignancies that relapse after allogeneic HPCT. This trial aims to evaluate the safety and efficacy of treatment with the anti-viral drug, Peg-Interferon, in patients with relapsed haematological malignancy after allogeneic haematopoietic progenitor cell transplantation (HPCT). Who is it for? You may be eligible to join this study if you are aged between 18 and 65 years old. Trial details Patients will initially have their immunosuppression withdrawn, and in the presence of frank haematological relapse, also undertake FLAG induction chemotherapy as a platform to provide both short-term disease control as well as lymphodepletion. In the absence of development of subsequent GVHD, Peg-Interferon will commence at a dose of 45mcg subcutaneouly once per week, with weekly escalation of dose to 90mcg, then 135mcg then 180mcg if tolerated. Patients will then continue peg-IFN as “maintenance” at 180mcg weekly for a total of 6 months (calculated from first dose of peg-IFN) if able. If after achieving maximal doses of pegylated-IFN (180mcg/week) significant GVHD has not developed, depending on donor availability, patients will also be eligible to commence donor lymphocyte infusions (DLI) whilst continuing pegylated-IFN. This approach will (i) permit the use of chemotherapy without the induction of severe GVHD that is seen in the majority of patients that receive a second stem cell graft (ii) whilst permitting peg-IFN to be delivered to the majority of recipients and (iii) allowing DLI to be administered thereafter to poor responders. Participants will be assessed at 2 years following enrolment to determine how they responded to this treatment.
Eligibility
Inclusion Criteria10
- Patients with relapse of their primary disease after allogeneic HPCT (either sibling or VUD donors).
- Age greater than or equal to 18 years and less than 70 years
- Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >50%)
- Off immune suppression:
- Patients are allowed to continue on prednisolone (or equivalent) at doses <0.5mg/kg/day.
- Patients must have ceased Cyclosporine (CSA), Tacrolimus (Tacro), Mycophenolate Mofetil (MMF) and / or all other immunosuppressants
- Absence of active significant graft versus host disease off immunosupression defined by less than grade 2 acute graft vesus host disease and or progressive or extensive stage chronic graft versus host disease.
- Adequate organ function for FLAG chemotherapy:
- Total Bilirubin less than or equal to 30umol/L
- Creatinine clearance less than or equal to 50ml/min/1.73m^2 for patients with creatinine levels above ULN
Exclusion Criteria10
- Inadequate organ function for FLAG chemotherapy (if in haematological relapse):
- Total Bilirubin >30umol/L
- Creatinine Clearance < 50ml/min/1.73m^2 for patients with creatinine levels above ULN
- Active acute (grade II-IV) or progressive and / or extensive stage chronic GVHD requiring immune suppression with prednisone (or equivalent) at doses >0.5mg/kg/day or ongoing therapy with other immunosuppressant medications including calcineurin inhibitors (cyclosporine, Tacrolimus) and MMF.
- Patients receiving any other investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, uncontrolled hypertension or heart failure, uncontrolled diabetes, uncontrolled autoimmune disease (especially thyroid), uncontrolled COPD, uncontrolled depression, epilepsy and social situations that would limit compliance with study requirements.
- Known HIV infection.
- Pregnant or breastfeeding, or patient with reproductive potential who is not willing to use adequate contraceptive precautions in the judgement of the Investigator. Adequate contraception is defined as a double-barrier method, i.e. using at least 2 methods of contraception e.g. 2 actual barrier methods or 1 actual barrier method and 1 hormonal method.
- Donor is an identical twin (i.e. syngeneic)
- History of allergic or grade IV reactions to interferon, including known allergies to E coli-derived products eg. G-CSF.
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Interventions
Pegasys"Registered Trademark" is a recombinant interferon-2alpha protein produced by recombinant DNA technology within E coli and then conjugated to a polyethylene glycol chain (PEG) molecule of 40 kilodaltons. Pegylation of the native IFN molecule eliminates renal excretion and prolongs the drug half-live from 3-4 hours to 160 hours after subcutaneous dosing, reaching steady state in 5-8 weeks. For this reason pegylation of IFN results in prolonged action and avoids the need for the daily dosing required for the native cytokine and the frequent peak and troughs seen therein. In general pegylation of cytokines result in significantly prolonged activity and enhanced potency in vivo. Pegasys"Registered Trademark" will commence at a dose of 45mcg subcutaneously once per week, with weekly escalation of dose to 90mcg, then 135mcg then 180mcg if tolerated. Patients will then continue peg-IFN as “maintenance” at 180mcg weekly for a total of 6 months (calculated from first dose of peg-IFN) if able. Importantly, the administration of pegylated-IFN after allogeneic BMT has not been studied previously.
Locations(1)
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ACTRN12612000728831