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

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.

Study Overview

• Status: Completed
• Conditions: Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)
• Intervention / Treatment: Drug: Everolimus

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Wiesbaden, Hessen, Germany, 65191
      • Zentrum für Knochenmark- und Blutstammzelltransplantation,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Everolimus; All patients will be given everolimus and the magnitude of the side effects will be measured

Drug: 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; Other Names: Everolimus: Certican®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
• Collaborators: ClinAssess GmbH; Deutsche Klinik fuer Diagnostik
• Investigators: Principal Investigator: Michael Schleuning, Prof. Dr. med., Stiftung Deutsche Klinik für Diagnostik GmbH

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2011
• Primary Completion (ACTUAL): April 30, 2016
• Study Completion (ACTUAL): April 30, 2016

Study Registration Dates

• First Submitted: January 3, 2012
• First Submitted That Met QC Criteria: January 10, 2012
• First Posted (ESTIMATE): January 13, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: Ev02 (Everolimus-GvHD); 2010-023630-24 (EUDRACT_NUMBER)