Bortezomib and Reduced Intensity Allogenic Stem Cell Transplantation for Lymphoid Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00439556
First received: February 22, 2007
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Lymphoma
Drug: Carmustine
Drug: Cytarabine
Drug: Etoposide
Drug: Melphalan
Drug: Rituximab
Drug: Bortezomib
Other: Allogeneic Stem Cell Infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bortezomib (Velcade) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of Bortezomib [ Time Frame: 90 days after the start of treatment ] [ Designated as safety issue: No ]
    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:
  • Incidence of Graft-Versus-Host Disease (GVHD) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Cumulative incidence of acute GVHD and chronic GVHD examined using method of Gooley Gooley, T.A., Leisenring, W., Crowley, J., Storer, B.E., "Estimation of failure probabilities in the presence of competing risks: new representations of old estimators", Statistics in Medicine, 18: 695-706 (1999). et al as disease recurrence or death without GVHD are competing risks. GVHD rates also compared to historical controls.


Estimated Enrollment: 52
Study Start Date: February 2007
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Cystosine 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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439556

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Issa F. Khouri, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00439556     History of Changes
Other Study ID Numbers: 2006-0066, NCI-2010-00579
Study First Received: February 22, 2007
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
Bortezomib
Velcade
LDP-341
MLN341
PS-341
Carmustine
Cytarabine
Etoposide
Melphalan
Rituximab
BEAM
BCNU
BiCNU®
ARA-C
Cytosar
DepoCyt®
Cytosine arabinosine hydrochloride
VePesid®
Rituxan

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Melphalan
Etoposide phosphate
Rituximab
Bortezomib
Cytarabine
Etoposide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014