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Vorinostat to Prevent Graft Versus Host Disease Following Reduced Intensity, Related Donor Stem Cell Transplant

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00810602
First Posted: December 18, 2008
Last Update Posted: April 11, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Pavan Reddy, MD, University of Michigan Cancer Center
Results First Submitted: November 27, 2013  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Hematologic Malignancies
Graft vs Host Disease
Interventions: Procedure: reduced intensity, related donor stem cell transplant
Drug: tacrolimus (standard GVHD prophylaxis)
Drug: mycophenolate (standard GVHD prophylaxis)
Drug: vorinostat

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
From March 2008 through February 2013, eligible patients with advanced hematological cancers were enrolled at the University of Michigan and Washington University in St. Louis.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All patients received a preparative regimen of intravenous fludarabine (40 mg/m2 on day -5 through day -2) and busulfan (3.2 mg/kg on days -5 and -4) (FluBu2) followed by the infusion of peripheral blood stem cells (PBSC) on day 0. GVHD prophylaxis consisted of tacrolimus initiated on day -3 and mycophenolate mofetil (MMF) on day 0 through day 28.

Reporting Groups
  Description
Phase 1 In the Phase 1 portion of the study, participants were administered Vorinostat, either 100 mg or 200mg, twice daily, orally, starting ten days prior to the stem cell infusion and continuing through day 100 post-HSCT. If tolerated, vorinostat will be continued until day 100 post-transplant,whether or not acute GVHD develops.
Phase 2 100 mg was selected as the Phase 2 dose. Participants were administered Vorinostat, 100 mg, twice daily, orally, starting ten days prior to the stem cell infusion and continuing through day 100 post-HSCT. If tolerated, vorinostat will be continued until day 100 post-transplant,whether or not acute GVHD develops.

Participant Flow:   Overall Study
    Phase 1   Phase 2
STARTED   27   34 
COMPLETED   19   31 
NOT COMPLETED   8   3 
Withdrawal by Subject                8                3 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Only participants that completed 21 days of vorinostat were considered evaluable for both toxicity and the primary outcome, therfore only 50 of the 61 patients initially enrolled are represented in baseline characteristics.

Reporting Groups
  Description
Vorinostat Prophylaxis

Vorinostat, combined with standard GVHD prevention medications(tacrolimus, mycophenolate) for adults who received a reduced intensity, related donor stem cell transplant.

Vorinostat was administered daily starting ten days prior to the stem cell infusion and continued through day 100 post-HSCT. If tolerated, vorinostat will be continued until day 100 post-transplant,whether or not acute GVHD develops.

The phase 1 portion of the study tested two doses of vorinostat, 100 mg BID and 200 mg BID.The first ten patients received vorinostat 100 mg BID, followed by nine patients who received the 200 mg BID dose.

Although no dose-limiting toxicities were reached at the 200 mg BID dose, there was an increased incidence of protocol-driven dose modifications, primarily due to non-symptomatic thrombocytopenia after engraftment. Consequently, the 100 mg BID dose was selected as the phase 2 dose for the remaining patients.


Baseline Measures
   Vorinostat Prophylaxis 
Overall Participants Analyzed 
[Units: Participants]
 50 
Age 
[Units: Years]
Median (Full Range)
 59 
 (43 to 69) 
Gender [1] 
[Units: Participants]
 
Female   22 
Male   28 
[1] (44%, 56% of evaluable subjects, respectively)
Ethnicity (NIH/OMB) 
[Units: Participants]
 
Hispanic or Latino   2 
Not Hispanic or Latino   46 
Unknown or Not Reported   2 
Diagnosis 
[Units: Participants]
 
Acute myelogenous leukemia   19 
Myelodysplastic syndrome   10 
Non-Hodgkin's lymphoma   12 
Chronic lymphocytic leukemia   4 
Myeloproliferative disorder or myelofibrosis   4 
Acute biphenotypic leukemia   1 
Disease Status 
[Units: Participants]
 
Low   25 
Intermediate   20 
High   5 
Comorbidity index [1] 
[Units: Participants]
 
Low   8 
Intermediate   15 
High   27 
[1] Hematopoietic Cell Transplant – Comorbidity Index: Low = 0, Intermediate = 1 or 2, High ≥ 3
Donor Type 
[Units: Participants]
 
Matched related   46 
One-antigen mismatched related   4 
CMV Status [1] 
[Units: Participants]
 
Recipient or Donor positive (detailed below)   30 
R+, D+   17 
R-, D+   6 
R+, D-   7 
Recipient and Donor negative   20 
[1] Recipient(R),Donor (D), positive (+), negative(-)
CD34+ Count (10^6 cells/kg) 
[Units: Count (10^6 cells/kg)]
Median (Full Range)
 5.0 
 (1.9 to 8) 
Engraftment Day [1] 
[Units: Days]
Median (Full Range)
 
Neutrophil   12 
 (8 to 19) 
Platelet   12 
 (9 to 30) 
[1] Median time to platelet and neutrophil engraftment.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   100-day Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GVHD)   [ Time Frame: 100 days ]

2.  Secondary:   Number of Serious Adverse Events   [ Time Frame: 100 days ]

3.  Secondary:   Percent Cumulative Incidence of Relapse at 2 Years.   [ Time Frame: two years ]

4.  Secondary:   Percent Survival at 2-years   [ Time Frame: two years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr. Sung Choi
Organization: University of Michigan Comprehensive Cancer Center
phone: 734-764-8630
e-mail: sungchoi@med.umich.edu


Publications of Results:

Responsible Party: Pavan Reddy, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00810602     History of Changes
Other Study ID Numbers: UMCC 2008.095
First Submitted: December 17, 2008
First Posted: December 18, 2008
Results First Submitted: November 27, 2013
Results First Posted: April 11, 2014
Last Update Posted: April 11, 2014