Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Hematopoietic Stem Cell Transplantation

October 20, 2014 updated by: Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute

Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation

This trial will test the hypothesis that the combination of sirolimus, mycophenolate mofetil, and bortezomib will be effective in preventing both acute and chronic GVHD after reduced intensity allogeneic stem cell transplantation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The combination of tacrolimus and methotrexate is standard therapy for prevention of GVHD, however, our recent experience has demonstrated that the substitution of sirolimus for methotrexate provides superior GVHD control with reduced transplant-related toxicity. One limitation to the use of calcineurin inhibitors in GVHD prevention is the disruption in Treg function and proliferation. Based on our evolving understanding of the role of Treg in the development of chronic GVHD, we propose a GVHD prophylactic regimen that is effective in prevention of acute GVHD, but by virtue of the maintenance of Treg activity may be able to prevent chronic GVHD. We hypothesize that the substitution of mycophenolate mofetil for tacrolimus as well as the addition of bortezomib may provide similar protection against acute GVHD and prevent chronic GVHD while minimizing renal toxicity after transplantation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with hematologic malignancies, who are at high risk of complications after conventional myeloablative transplantation
  2. Patients must have a 6/6 matched, related donor. Matching at HLA Class II will be based on PCR of sequence specific primers (SSP). Among family member transplants, serologic matching at Class I is sufficient
  3. Patient age greater than 18
  4. Performance status 0-2
  5. Life expectancy of > 100 days without transplantation
  6. Written informed consent must be obtained in all cases from the patient

Exclusion Criteria:

  1. Pregnancy
  2. Prior Allogeneic Stem Cell Transplantation from any donor
  3. Evidence of HIV infection or active Hepatitis B or C infection
  4. Heart failure uncontrolled by medications
  5. Total bilirubin > 2.0 mg/dl that is due to hepatocellular dysfunction
  6. AST > 90
  7. Cholesterol > 300 mg/dl or Triglycerides > 400 mg/dl while adequately treated
  8. Uncontrolled bacterial, viral or fungal infection
  9. Requirement for voriconazole at the time of hospital admission

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Siro/MMF
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF)
Drug: Mycophenolate mofetil
Other Names:
  • Cellcept
Drug: Sirolimus
Other Names:
  • Rapamycin
Experimental: Siro/MMF/Bort
Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) *added with study reopening in 2012
Drug: Mycophenolate mofetil
Other Names:
  • Cellcept
Drug: Bortezomib
Other Names:
  • Velcade
Drug: Sirolimus
Other Names:
  • Rapamycin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To Determine the Rate of Grade II-IV Acute GVHD When Sirolimus and Mycophenolate Mofetil or Sirolimus, Mycophenolate Mofetil and Bortezomib is Used for GVHD Prophylaxis After Allogeneic Stem Cell Transplantation in Patients With Hematologic Malignancies
Time Frame: 150 days
150 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 1 year
1 year
Donor Stem Cell Engraftment, Including Donor-host Hematopoietic Chimerism Studies Post Transplant
Time Frame: 30 days
Engraftment of donor cells by week 4 after transplantation. Assessment of donor stem cell engraftment will include donor-host hematopoietic chimerism analyses at 4 weeks and every 3 months after transplantation. Chimerism measured from peripheral blood or from bone marrow.
30 days
The Rate of Renal Insufficiency
Time Frame: 1 year

Renal function will be measured weekly after transplant for 4 weeks, at 8 weeks and then at 3 month intervals from transplantation. Sentinel renal events such as the occurrence of thrombotic microangiopathy will be noted.

The rationale for the substitution of mycophenolate mofetil for tacrolimus is to continue to prevent acute GVHD, but minimize renal toxicity after transplantation. We will thus monitor renal toxicity closely in this study. In our previous experience, the rate of grade III-V renal toxicity by day 100 after transplantation was about 10%. Here, grade III is defined as a creatinine level between 3.1 to 6 times the normal level, grade IV is defined as a creatinine level 6 times or more the normal level, and grade V is defined as a fatality due to renal toxicity.
1 year
To Correlate the Serum Concentrations of Mycophenolate Mofetil and Its Metabolites With Acute GVHD Incidence
Time Frame: 1 year
This outcome measure was presented as a comparison between incidence of Grade 0-I aGVHD and Grade II-IV aGVHD across 5 time points (Weeks 1,2,3,8, and 12).
1 year
Incidence of 100 Day Mortality
Time Frame: 100 days
100 days
Incidence of Chronic GVHD
Time Frame: 1 year

Chronic GVHD will be graded according to the modified Seattle criteria. Chronic GVHD divided into limited and extensive and evaluated across the following systems: skin, cutaneous structures, liver, mouth, eyes, esophagus, intestines, lung, musculoskeletal, serous, nervous, urologic, vagina, hematopoietic, and immune.

Localized skin involvement with or without hepatic dysfunction is classified as limited disease.

Generalized skin involvement or limited disease plus eye involvement, oral involvement, hepatic dysfunction with abnormal liver histology, or involvement of any other target organ was classified as extensive disease.

Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant.

2003;9:215-33.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dana-Farber Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Wyeth is now a wholly owned subsidiary of Pfizer
PDL BioPharma, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Corey Cutler, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 23, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 21, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DFCI 07-197

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Graft-vs-Host Disease

Clinical Trials on Mycophenolate mofetil

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings