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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Deutsche Klinik fuer Diagnostik
ClinAssess GmbH
Information provided by (Responsible Party):
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier:
NCT01509560
First received: January 3, 2012
Last updated: March 13, 2013
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH:

Primary Outcome Measures:
  • Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]

    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


Secondary Outcome Measures:
  • Adverse drug reactions on Everolimus [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
    • Adverse drug reactions on Everolimus
    • Frequency and grading of GvHD (according to NIH concerns) and POLT
    • Lung function score (LFS)
    • Overall survival


Estimated Enrollment: 25
Study Start Date: November 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Everolimus: Certican®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01509560

Contacts
Contact: Michael Schleuning, Prof. Dr. med. +49 611 577 ext 169 schleuning.kmt@dkd-wiesbaden.de
Contact: Rainer Schwerdtfeger, PD Dr. med. +49 611 577 ext 169 schwerdtfeger.kmt@dkd-wiesbaden.de

Locations
Germany
Zentrum für Knochenmark- und Blutstammzelltransplantation, Recruiting
Wiesbaden, Hessen, Germany, 65191
Contact: Michael Schleuning, Prof. Dr. med.    +49 611 577 ext 169    schleuning.kmt@dkd-wiesbaden.de   
Contact: Rainer Schwerdtfeger, PD Dr. med.    +49 611 577 ext 169    schwerdtfeger.kmt@dkd-wiesbaden.de   
Principal Investigator: Michael Schleuning, Prof. Dr. med.         
Sponsors and Collaborators
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
Deutsche Klinik fuer Diagnostik
ClinAssess GmbH
Investigators
Principal Investigator: Michael Schleuning, Prof. Dr. med. Stiftung Deutsche Klinik für Diagnostik GmbH
  More Information

No publications provided

Responsible Party: Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier: NCT01509560     History of Changes
Other Study ID Numbers: Ev02 (Everolimus-GvHD), 2010-023630-24
Study First Received: January 3, 2012
Last Updated: March 13, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 10, 2014