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

This study is currently recruiting participants.

Verified January 2012 by Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH

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

History of Changes

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:

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

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®

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

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 May 16, 2013

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