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Bortezomib and Chemotherapy in Treating Participants With Lymphoid Malignancies Undergoing Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT00439556
Recruitment Status : Completed
First Posted : February 23, 2007
Results First Posted : August 13, 2019
Last Update Posted : September 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE February 22, 2007
First Posted Date  ICMJE February 23, 2007
Results First Submitted Date  ICMJE July 26, 2019
Results First Posted Date  ICMJE August 13, 2019
Last Update Posted Date September 10, 2019
Actual Study Start Date  ICMJE February 13, 2007
Actual Primary Completion Date June 7, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
  • Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: From start of treatment to 90 days after the start of treatment ]
    To determine the maximum tolerated dose(MTD) of velcade and dose limiting toxicity(DLT). A dose limiting toxicity (DLT) was defined as a grade 3-4 neurological toxicity, graft failure, or death due to GvHD. The Commom Terminlogy Criteria for Adverse Events v3.0 was used.
  • Disease-free Survival [ Time Frame: At 1 year ]
    To determine DFS at 1 year post transplant.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bortezomib and Chemotherapy in Treating Participants With Lymphoid Malignancies Undergoing Stem Cell Transplant
Official Title  ICMJE Bortezomib (Velcade®) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies
Brief Summary This phase II trial studies the side effects and best dose of bortezomib when given with chemotherapy and to see how well they work in treating participants with lymphoid malignancies undergoing stem cell transplant. Giving chemotherapy before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving tacrolimus and methotrexate after the transplant may stop this from happening. Giving bortezomib and chemotherapy may work better in treating participants with lymphoid malignancies undergoing a stem cell transplant.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Velcade (bortezomib) in patients with lymphoid malignancies undergoing allogeneic peripheral blood stem cell or bone marrow transplantation.

II. To determine the 1-year disease-free-survival (DFS) and the toxicity profile of Velcade (bortezomib) in patients with lymphoid malignancies undergoing allogeneic peripheral blood stem cell or bone marrow transplantation.

SECONDARY OBJECTIVES:

I. To compare the incidence of graft versus host disease (GVHD) with historical controls.

OUTLINE: This is a dose-escalation study of bortezomib.

Participants receive carmustine intravenously (IV) over 1 hour on day -6, cytarabine IV over 1 hour twice daily (BID) on days -5 to -2, etoposide IV over 3 hours BID on days -5 to -2, and melphalan IV over 30 minutes on day -1. Participants also receive rituximab IV on days -13, -6, +1, and +8, and bortezomib IV over 1 minute on days -13, -6, -1, and +2. Participants receiving a matched unrelated or mismatched donor transplant also receive anti-thymocyte globulin IV over 4-6 hours on days -6 and -5. Participants then undergo allogeneic hematopoietic stem cell transplantation over 30-45 minutes on day 0 and receive filgrastim subcutaneously (SC) once daily (QD) starting on day +7 until blood counts return to normal level. Participants receive tacrolimus IV starting on day -2 changing to orally (PO) before leaving the hospital for 6-8 months after the transplant. Participants also receive methotrexate IV over a few minutes on days +1, +3, and +6 and those receiving a matched unrelated or mismatched donor transplant also receive methotrexate IV on day +11.

After completion of study treatment, participants are followed up at 1 month, every 3 months for 1 year, and then every 6 months for 5 years.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • CD20 Positive
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Lymphocytic Neoplasm
  • Lymphoma
Intervention  ICMJE
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic hematopoietic stem cell transplantation
    Other Names:
    • Allogeneic Hematopoietic Cell Transplantation
    • Allogeneic Stem Cell Transplantation
    • HSC
    • HSCT
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
    • Antithymocyte Globulin
    • Antithymocyte Serum
    • ATG
    • ATGAM
    • ATS
    • Thymoglobulin
  • Drug: Bortezomib
    Given IV
    Other Names:
    • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
    • LDP 341
    • MLN341
    • PS-341
    • PS341
    • Velcade
  • Drug: Carmustine
    Given IV
    Other Names:
    • BCNU
    • Becenum
    • Becenun
    • BiCNU
    • Bis(chloroethyl) Nitrosourea
    • Bis-Chloronitrosourea
    • Carmubris
    • Carmustin
    • Carmustinum
    • FDA 0345
    • Gliadel
    • N,N'-Bis(2-chloroethyl)-N-nitrosourea
    • Nitrourean
    • Nitrumon
    • SK 27702
    • SRI 1720
    • WR-139021
  • Drug: Cytarabine
    Given IV
    Other Names:
    • .beta.-Cytosine arabinoside
    • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-.beta.-D-Arabinofuranosylcytosine
    • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-Beta-D-arabinofuranosylcytosine
    • 1.beta.-D-Arabinofuranosylcytosine
    • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    • Alexan
    • Ara-C
    • ARA-cell
    • Arabine
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Aracytidine
    • Aracytin
    • Aracytine
    • Beta-cytosine Arabinoside
    • CHX-3311
    • Cytarabinum
    • Cytarbel
    • Cytosar
    • Cytosine Arabinoside
    • Cytosine-.beta.-arabinoside
    • Cytosine-beta-arabinoside
    • Erpalfa
    • Starasid
    • Tarabine PFS
    • U 19920
    • U-19920
    • Udicil
    • WR-28453
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Biological: Filgrastim
    Given SC
    Other Names:
    • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
    • G-CSF
    • Neupogen
    • r-metHuG-CSF
    • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
    • rG-CSF
    • Tevagrastim
  • Drug: Melphalan
    Given IV
    Other Names:
    • Alanine Nitrogen Mustard
    • CB-3025
    • L-PAM
    • L-Phenylalanine Mustard
    • L-sarcolysin
    • L-Sarcolysin Phenylalanine mustard
    • L-Sarcolysine
    • Melphalanum
    • Phenylalanine Mustard
    • Phenylalanine nitrogen mustard
    • Sarcoclorin
    • Sarkolysin
    • WR-19813
  • Drug: Methotrexate
    Given IV
    Other Names:
    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS
    • Lantarel
    • Ledertrexate
    • Lumexon
    • Maxtrex
    • Medsatrexate
    • Metex
    • Methoblastin
    • Methotrexate LPF
    • Methotrexate Methylaminopterin
    • Methotrexatum
    • Metotrexato
    • Metrotex
    • Mexate
    • Mexate-AQ
    • MTX
    • Novatrex
    • Rheumatrex
    • Texate
    • Tremetex
    • Trexeron
    • Trixilem
    • WR-19039
  • Biological: Rituximab
    Given IV
    Other Names:
    • ABP 798
    • BI 695500
    • C2B8 Monoclonal Antibody
    • Chimeric Anti-CD20 Antibody
    • CT-P10
    • IDEC-102
    • IDEC-C2B8
    • IDEC-C2B8 Monoclonal Antibody
    • MabThera
    • Monoclonal Antibody IDEC-C2B8
    • PF-05280586
    • Rituxan
    • Rituximab Biosimilar ABP 798
    • Rituximab Biosimilar BI 695500
    • Rituximab Biosimilar CT-P10
    • Rituximab Biosimilar GB241
    • Rituximab Biosimilar IBI301
    • Rituximab Biosimilar PF-05280586
    • Rituximab Biosimilar RTXM83
    • Rituximab Biosimilar SAIT101
    • RTXM83
  • Drug: Tacrolimus
    Given IV and PO
    Other Names:
    • FK 506
    • Fujimycin
    • Hecoria
    • Prograf
    • Protopic
Study Arms  ICMJE Experimental: Treatment (chemotherapy, transplant, filgrastim, tacrolimus)
See Detailed Description
Interventions:
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Biological: Anti-Thymocyte Globulin
  • Drug: Bortezomib
  • Drug: Carmustine
  • Drug: Cytarabine
  • Drug: Etoposide
  • Biological: Filgrastim
  • Drug: Melphalan
  • Drug: Methotrexate
  • Biological: Rituximab
  • Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2018)		 40
Original Enrollment  ICMJE
 (submitted: February 22, 2007)		 52
Actual Study Completion Date  ICMJE June 7, 2018
Actual Primary Completion Date June 7, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Any histological subtype of CD20+ lymphoid malignancies or T-cell lymphoid malignancies.
  • 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 International Prognostic Index [IPI] of >= 2).
  • Patients with prior non-myeloablative transplant are eligible if not from the same donor.
  • A fully-matched or one-antigen mismatched sibling or unrelated donor.
  • Left ventricular ejection fraction (EF) >= 40% with no uncontrolled arrhythmias or symptomatic heart disease.
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 40%.
  • Serum creatinine < 1.8 mg/dL.
  • Serum bilirubin < 3 X upper limit of normal.
  • Serum glutamate pyruvate transaminase (SGPT) < 3 X upper limit of normal.
  • Voluntary signed, written Institutional Review Board (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.
  • 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:

  • Past history of anaphylaxis following exposure to rituximab or Velcade, boron or mannitol.
  • History of grade 3 or 4 National Cancer Institute (NCI) toxicity with prior Velcade therapy.
  • Patient with active central nervous system (CNS) disease.
  • Pregnant (positive beta human chorionic gonadotropin [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.
  • Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV-I), hepatitis B, or hepatitis C.
  • Patients with other malignancies diagnosed within 2 years prior to study day -13 (except skin squamous or basal cell carcinoma).
  • Active uncontrolled bacterial, viral or fungal infections.
  • Major surgical procedure or significant traumatic injury within 4 weeks prior to day -13.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to day -13.
  • History of stroke within 6 months.
  • 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 arrhythmia, unstable angina, uncontrolled congestive heart failure or arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by investigator as not medically relevant.
  • Uncontrolled hypertension (>= 140/90).
  • Uncontrolled chronic diarrhea.
  • A prior allogeneic transplant from the same donor.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patient has received other investigational drugs within 3 weeks before enrollment.
  • Active peripheral neuropathy greater or equal to grade 2.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00439556
Other Study ID Numbers  ICMJE 2006-0066
NCI-2018-01830 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2006-0066 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Issa Khouri M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP