PhaseII,Open-label,Pilot Study Evaluating the Safety+Effi... | NCT01509560

NCT01509560

ID	Type	Description	Link
2010-023630-24	EudraCT Number

Status Module

Name	Class
Deutsche Klinik fuer Diagnostik	OTHER
ClinAssess GmbH	INDUSTRY

Oversight Module

Arms/Interventions Module

Label	Type	Description	Intervention Names
Everolimus	Experimental	All patients will be given everolimus and the magnitude of the side effects will be measured	Drug: Everolimus

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Everolimus	Drug	Start therapy: 2x 0.75 mg/day (morning and evening) to receive a serum trough level of 3 - 5 ng/ml. First evaluation of Everolimus serum level 3-7 days after start of therapy, second 7 days later, subsequently on study weeks 4, 6, 9, 12 and 16. Dose has to be adapted if trough level exceeds 5 ng/ml. As soon as Everolimus trough level exceeds 3 ng/ml after start of therapy, calineurine inhibitors (e.g. cyclosporine) will be reduced: halve of the dose for the 3 consecutive days, withdrawal on day 4. Prednisone will be reduced accordingly (a 22 weeks scheme is recommended) Everolimus will be used for 98 days or 14 weeks, as described above Everolimus therapy might be extended (independently of the study) if the patient suffering from milde chronic GvHD (according to NIH criteria) or milde PTOLD and lung function score is not reduced more than 25% since begin of Everolimus therapy Everolimus will be reduced to 50% of the dosage for 2 weeks before withdraw (normally weeks 15 and 16

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus	Primary endpoint Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus Reasons for withdrawal of Everolimus treatment: Unacceptabel toxicity Therapy failure: Recurrence of moderate or severe chronic GvHD (according to NIH criteria), clearly differentiated from acute forms of GvHD Reduction of LFS of more than 25% compared to the last value within 14 days before Everolimus treatment Therapy with immunosuppressive drugs in addition to Everolimus	16 months

Secondary Outcomes

Measure	Description	Time Frame
Adverse drug reactions on Everolimus	Adverse drug reactions on Everolimus Frequency and grading of GvHD (according to NIH concerns) and POLT Lung function score (LFS) Overall survival	16 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients after allogeneic stem cell transplantation aged ≥ 18 years
Prophylaxes of GvHD with calcineurin inhibitors (Ciclosporine A, Tacrolimus) and MTX or MMF (previous therapy of acute GvHD with additional prednisone is permitted)
Increased risk of chronic GvHD, defined by
Male with female donor
HLA mismatch class I- or II towards GvHD
Persistant active acute GvHD on day +50 after stem cell transplantation despite of high-dose steroids and cyclosporine
Reduction of baseline FEV1 or DLCO (examined 0 - 50 days before transplantation) of ≥ 25%
New occurrence of acute GvHD between day +50 and +100 after stem cell transplantation
Informed concent

Exclusion Criteria:

Use (prophylactic or therapeutic) of mTor inhibitors after SCT
Overlap of acute and chronic GvHD
Total cholesterol ≥ 3-fold of upper limit (UL) or triglycerides ≥ 3-fold UL
GOT, GPT, Bilirubin ≥ 3-fold UL (if not related to GvHD)
Creatinine ≥ 3-fold UL
Confirmed active hepatitis B or C
All circumstances where impaired wound healing might be a risk factor, esp. surgical interventions in the last weeks, ulcers of skin or mucosa
Known intolerance to Everolimus, Sirolimus or other compoments of Certican®
Lactose intolerance
Pregnancy or lactation
Women in reproductive age, except of women with the following criteria:
Postmenopausal (12 month natural amenorrhea)
Postoperativ (≥ 6 months after bilateral ovariectomy with / without hysterectomy)
During therapy and at least 6 months after the last application of Everolimus: regular and correct high-effective contraception (Pearl-Index < 1; e. g. oral contraception, intrauterine device, implantate, contraceptive patch, combination of barrier methods (condom and cervical cap/diaphragm), abstinence
Men, not using one of the following methods of contraception during therapy and at least 6 month after the last application of Everolimus:
Sexual abstinence
Vasectomy
Condom
Impairments or diseases reducing the ability of informed consent
Participation of another study (e.g. for prophylactic immunsuppression in the stem cell transplantation procedure) within the last 60 day before recruitment