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

NCT01509560 | Completed Phase 2

• 2 other identifiers: Ev02 (Everolimus-GvHD)2010-023630-24
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (1)

• 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 (1)

• Adverse drug reactions on Everolimus

  16 months

Study Arms (1)

Everolimus

EXPERIMENTAL

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

Drug: Everolimus

Interventions

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

Also known as: Everolimus: Certican®

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH: lead
• Deutsche Klinik fuer Diagnostik: collaborator
• ClinAssess GmbH: collaborator

Study Sites (1)

Zentrum für Knochenmark- und Blutstammzelltransplantation,

Wiesbaden, Hesse, 65191, Germany

Location

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Michael Schleuning, Prof. Dr. med.

  Stiftung Deutsche Klinik für Diagnostik GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2012
• First Posted: January 13, 2012
• Study Start: November 1, 2011
• Primary Completion: April 30, 2016
• Study Completion: April 30, 2016
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

DE (1)