PhaseII,Open-label,Pilot Study Evaluating the Safety+Efficacy of Certican ® in the Prevention of Chronic Graft-versus-host Disease+Late Pulmonary Complications After Allogeneic Hematopoietic Cell Transplantation Blood

NCT ID: NCT01509560

Last Updated: 2017-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-01
• Study Completion Date: 2016-04-30

Brief Summary

In this prospective study is to examine whether the use of everolimus in patients after allogeneic SCT as part of GVHD prophylaxis for a further review in clinical studies is appropriate.

Conditions

Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus

All patients will be given everolimus and the magnitude of the side effects will be measured

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: 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

Interventions

Everolimus

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

Intervention Type: DRUG

Other Intervention Names

Everolimus: Certican®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsche Klinik fuer Diagnostik

OTHER

Sponsor Role: collaborator

ClinAssess GmbH

INDUSTRY

Sponsor Role: collaborator

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Schleuning, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Stiftung Deutsche Klinik für Diagnostik GmbH

Locations

Zentrum für Knochenmark- und Blutstammzelltransplantation,

Wiesbaden, Hesse, Germany

Countries

Germany

Other Identifiers

2010-023630-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Ev02 (Everolimus-GvHD)

Identifier Type: -

Identifier Source: org_study_id