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

NCT00439556 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 2006-0066NCI-2018-01830P30CA016672
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

CD20 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Lymphocytic Neoplasm; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity (DLT)

  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.

  From start of treatment to 90 days after the start of treatment

• Disease-free Survival

  To determine DFS at 1 year post transplant.

  At 1 year

Study Arms (1)

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

EXPERIMENTAL

See Detailed Description

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplantation

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Bortezomib DRUG

Given IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Carmustine DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Cytarabine DRUG

Given IV

Also known as: .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

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Filgrastim BIOLOGICAL

Given SC

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Methotrexate DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (chemotherapy, transplant, filgrastim, tacrolimus)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma

Interventions

Antilymphocyte Serum; thymoglobulin; Bortezomib; Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; Melphalan; Methotrexate; merphos; Rituximab; CT-P10; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Khouri,Issa,M.D. / Stem Cell Transplantation
• Organization: UT MD Anderson Cancer Center

ikhouri@mdanderson.org

713-792-8750

Study Officials

• Issa Khouri

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2007
• First Posted: February 23, 2007
• Study Start: February 13, 2007
• Primary Completion: June 7, 2018
• Study Completion: June 7, 2018
• Last Updated: September 10, 2019
• Results First Posted: August 13, 2019

Record last verified: 2019-08

Locations

US (1)