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Phase 2 Completed N=13 Prevention

Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation

Source: ClinicalTrials.gov NCT00369226 ↗
Enrolled (actual)
13
Serious AEs
15.6%
Results posted
Jul 2013
Primary outcomePrimary: The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation — 1.3 mg/m^2

Summary

The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation.

Outcome Measures

OutcomeResultp-value
PRIMARY
The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation
1.3
PRIMARY
Successful Initial Engraftment by Day 45 Post Peripheral Blood Stem Cell (PBSC) Infusion and Administration of Bortezomib (Velcade), Tacrolimus and Methotrexate
97
PRIMARY
Incidence of Grade II-IV Acute Graft Versus Host Disease (GVHD) by Day 100.
22
SECONDARY
Sustained Engraftment Following Transplant.
97
SECONDARY
Incidence of Chronic Graft Versus Host Disease (Chronic GVHD).
29
SECONDARY
Overall Survival and Progression-free Survival.
60; 76

Eligibility Criteria

Inclusion Criteria

  • Patients with hematologic malignancies including myelodysplastic syndrome (MDS), who are at a high risk of complications after myeloablative transplantation
  • Patients have a donor (both related and unrelated) who are mismatched according to protocol criteria
  • 18 years of age or older
  • Performance status 0-2
  • Life expectancy of > 100 days
  • Female subject is either post-menopausal or sterilized or willing to use an acceptable form of birth control
  • Male subject agrees to use an acceptable form of birth control

Exclusion Criteria

  • Evidence of HIV infection
  • Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction
  • Aspartate aminotransferase (AST) > 90
  • Known active hepatitis B or C
  • Serum creatinine > 2.0
  • Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment
  • Prior allogeneic stem cell transplant
  • Patients with myeloproliferative disease (e.g. myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia)
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Hypersensitivity to Velcade, boron or mannitol
  • Pregnant or breast feeding
  • Patient has received other investigational drugs 14 days before enrollment
  • Serious medical or psychiatric illness
  • Another active solid tumor malignancy at the time of study entry
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00369226). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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