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

NCT00369226 | Completed Phase 1 Results DMC

• 2 other identifiers: 06-065X05175
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hematologic Malignancies

Keywords

Velcade; Bortezomib; Allogeneic Stem Cell Transplant; GVHD

Outcome Measures

Primary Outcomes (3)

• 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

  The MTD of bortezomib was evaluated at 3 dose levels: Dose level 1: 1.0 mg/m\^2 Dose level 2: 1.3 mg/m\^2 Dose level 3: 1.5 mg/m\^2 Cohorts of 3-5 pts were enrolled at each dose level. At any dose level, if no DLT in the first 3, 4, or 5 pts, then dose escalation would occur. If 3 evaluable pts in cohort, and 1 of 3 experiences DLT then 2 additional pts treated at the same dose level. If \>=1 of 2 additional pts experience DLT then previous dose level will be MTD. If no DLT in additional 2 pts then dose escalation will occur. If 4 evaluable pts in cohort, and 1 of the 4 experiences DLT then 1 additional pt treated at same dose level. If this additional pt experiences DLT then the previous dose will be declared to be the MTD. If additional pt does not experience DLT, then dose escalation will take place. If 5 evaluable pts in cohort, and 1 experiences DLT, then dose escalation will take place. If \>=2 of first 3, 4, or 5 pts experience DLT then the previous dose will be declared MTD.

  by day 45 post PBSC infusion

• Successful Initial Engraftment by Day 45 Post Peripheral Blood Stem Cell (PBSC) Infusion and Administration of Bortezomib (Velcade), Tacrolimus and Methotrexate

  Percentage of participants who did not experience failure to engraft or relapse or death before assessment.

  by day 45 post PBSC infusion

• Incidence of Grade II-IV Acute Graft Versus Host Disease (GVHD) by Day 100.

  by day 100 after peripheral blood stem cell (PBSC) infusion

Secondary Outcomes (3)

• Sustained Engraftment Following Transplant.

  by day 100 post transplant

• Incidence of Chronic Graft Versus Host Disease (Chronic GVHD).

  by 1 year after PBSC infusion

• Overall Survival and Progression-free Survival.

  by 1 year after PBSC infusion

Study Arms (1)

Bortezomib/Tacrolimus/Methotrexate post HSCT

EXPERIMENTAL

Drug: Bortezomib (Velcade); Drug: Tacrolimus; Drug: Methotrexate; Procedure: blood stem cell transplantation

Interventions

Bortezomib (Velcade) DRUG

Infusion for a total of 3 doses

Bortezomib/Tacrolimus/Methotrexate post HSCT

Tacrolimus DRUG

Taken until Doctor determines it is not necessary any more

Bortezomib/Tacrolimus/Methotrexate post HSCT

Methotrexate DRUG

Infusion for a total of 4 doses

Bortezomib/Tacrolimus/Methotrexate post HSCT

blood stem cell transplantation PROCEDURE

Allogeneic Non-myeloablative peripheral blood stem cell transplantation

Bortezomib/Tacrolimus/Methotrexate post HSCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Koreth J, Stevenson KE, Kim HT, Garcia M, Ho VT, Armand P, Cutler C, Ritz J, Antin JH, Soiffer RJ, Alyea EP 3rd. Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors. Blood. 2009 Oct 29;114(18):3956-9. doi: 10.1182/blood-2009-07-231092. Epub 2009 Aug 27.

  PMID: 19713456 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Bortezomib; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: John Koreth, MBBS, D.Phil
• Organization: Dana-Farber Cancer Institute

jkoreth@partners.org

(617) 632-2949

Study Officials

• John Koreth, MD

  Dana-Farber Cance Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: August 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: September 1, 2011
• Last Updated: July 25, 2013
• Results First Posted: July 25, 2013

Record last verified: 2013-06

Locations

US (2)