Bortezomib and Reduced Intensity Allogenic Stem Cell Transplantation for Lymphoid Malignancies

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. Identifier: NCT00439556
Recruitment Status : Active, not recruiting
First Posted : February 23, 2007
Last Update Posted : February 22, 2018
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to find the highest tolerable dose of Velcade (bortezomib) that can be given with BEAM (carmustine, etoposide, cytarabine and melphalan) and rituximab in patients with lymphoma who receive a stem cell transplant.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Carmustine Drug: Cytarabine Drug: Etoposide Drug: Melphalan Drug: Rituximab Drug: Bortezomib Other: Allogeneic Stem Cell Infusion Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bortezomib (Velcade) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies
Study Start Date : February 2007
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Bortezomib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Bortezomib + Reduced Intensity Allo SCT

Bortezomib + BEAM (Carmustine, Etoposide, Cytarabine and Melphalan) + Rituximab

Allo SCT = Allogeneic Stem Cell Transplantation

Drug: Carmustine
300 mg/m^2 IV on Day -6
Other Names:
  • BCNU
  • BiCNU
Drug: Cytarabine
100 mg/m^2 IV twice a day x 4 Days (Days -5 through -2)
Other Names:
  • ARA-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Etoposide
100 mg/m^2 IV twice a day x 4 Days (Days -5 through -2)
Other Name: VePesid
Drug: Melphalan
100 mg/m^2 IV on Day -1
Drug: Rituximab
375 mg/m^2 IV on Day -13; 1000 mg/m^2 on Days -6, 1, & 8.
Other Name: Rituxan
Drug: Bortezomib
1.3 mg/m^2 IV on Days -13, -6, -1 and +2.
Other Names:
  • Velcade
  • LDP-341
  • MLN341
  • PS-341
Other: Allogeneic Stem Cell Infusion
Allogeneic Stem Cell Infusion administered on Day 0.
Other Names:
  • ASCT
  • Allogeneic Stem Cell Transplantation

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of Bortezomib [ Time Frame: 90 days after the start of treatment ]
    MTD defined as highest dose level at which 0/6 or 1/6 patients experience dose limiting toxicity (DLT). Dose limiting toxicity (DLT) defined as a grade 3-4 neurological toxicity, graft failure, or death due to GVHD.

Secondary Outcome Measures :
  1. 1-year disease free survival (DFS) rate [ Time Frame: 1 year ]
    Number of participants alive without disease progression one year from beginning treatment. Survival will be recorded by the day of death and the cause of death.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Up to 70 years of age.
  2. Any histological subtype of CD20+ lymphoid malignancies or T-cell lymphoid malignancies.
  3. Patients with CD20+ lymphoid malignancies in relapse after failing >/= 1 prior regimen of conventional treatment and not eligible for non-myeloablative transplant. Patients with T-Cell lymphoid malignancies can either be in relapse or newly diagnosed with high risk features (such as high IPI of >/= 2).
  4. Patients with prior non-myeloablative transplant are eligible if not from the same donor.
  5. A fully-matched or one-antigen mismatched sibling or unrelated donor.
  6. Left ventricular EF >/= 40% with no uncontrolled arrythmias or symptomatic heart disease..
  7. FEV1, FVC and DLCO >/= 40%.
  8. Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3X upper limit of normal,
  9. SGPT < 3X upper limit of normal.
  10. Voluntary signed, written IRB-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  11. Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  1. Past history of anaphylaxis following exposure to rituximab or VELCADE®, boron or mannitol
  2. History of grade 3 or 4 NCI toxicity with prior VELCADE® therapy
  3. Patient with active CNS disease.
  4. Pregnant (Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  5. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
  6. Patients with other malignancies diagnosed within 2 years prior to Study Day -13 (except skin squamous or basal cell carcinoma).
  7. Active uncontrolled bacterial, viral or fungal infections.
  8. Major surgical procedure or significant traumatic injury within 4 weeks prior to Day -13.
  9. Serious, non-healing wound, ulcer, or bone fracture.
  10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to Day -13.
  11. History of Stroke within 6 months.
  12. Myocardial infarction within the past 6 months prior to Study Day 1, or has New York Heart Association (NYHA) Class III or IV heart failure or arrythmia, unstable angina, uncontrolled congestive heart failure or arrythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.Prior to study entry, any ECG abnormality at screening must be documented by investigator as not medically relevant.
  13. Uncontrolled hypertension(>/=140/90) .
  14. Uncontrolled chronic diarrhea.
  15. A prior allogeneic transplant from the same donor.
  16. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  17. Patient has received other investigational drugs within 3 weeks before enrollment.
  18. Active peripheral neuropathy greater or equal to grade 2.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00439556

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Millennium Pharmaceuticals, Inc.
Principal Investigator: Issa F. Khouri, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00439556     History of Changes
Other Study ID Numbers: 2006-0066
NCI-2010-00579 ( Registry Identifier: NCI CTRP )
First Posted: February 23, 2007    Key Record Dates
Last Update Posted: February 22, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Cytosine arabinosine hydrochloride

Additional relevant MeSH terms:
Etoposide phosphate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists