Bortezomib, Rituximab and Combination Chemotherapy in Treating Participants With Mantle Cell Lymphoma

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-03

Study Completion Date

2020-10-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I/II trial studies the side effects and best dose of bortezomib when given with rituximab and chemotherapy drugs and to see how well they work in treating participants with mantle cell lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, dexamethasone, methotrexate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bortezomib, rituximab and combination chemotherapy may work better at treating mantle cell lymphoma.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Rituximab, Bortezomib,Bendamustine , Dexamethasone, Patients With Mantle Cell Lymphoma

NCT00740415

Lymphoma

COMPLETED PHASE2

Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)

NCT01439750

Mantle Cell Lymphoma

UNKNOWN PHASE1

Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

NCT00711828

Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Nodal Marginal Zone Lymphoma Recurrent Grade 1 Follicular Lymphoma +6 more

COMPLETED PHASE2

VELCADE in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

NCT00063713

Mantle Cell Lymphoma

COMPLETED PHASE2

Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma

NCT00310037

Mantle Cell Lymphoma

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyperCVAD) in patients with untreated aggressive mantle cell lymphoma. (Phase I) II. Evaluate the time to failure (TTF) rate following therapy with bortezomib plus rituximab-hyperCVAD alternating with bortezomib plus rituximab-high dose methotrexate/cytarabine in patients between 18 and 79 years of age with untreated aggressive mantle cell lymphoma. (Phase II)

SECONDARY OBJECTIVES:

I. Evaluate overall response rate, complete remission rate, overall survival, and duration of remission. (Phase I) II. Evaluate overall response rate, overall survival, and duration of remission. (Phase II) III. Evaluate toxicity of the combination regimen. (Phase II) IV. Correlate outcome with pretreatment markers. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study.

Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.

Drug Combination I: Participants receive rituximab intravenously (IV) over 6 hours on day 1, cyclophosphamide IV over 3 hours twice daily (BID) on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone orally (PO) or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.

Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

After completion of study treatment, participants are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mantle Cell Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (combination chemotherapy)

Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.

Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.

Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Group Type EXPERIMENTAL

Bortezomib

Intervention Type DRUG

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Dexamethasone

Intervention Type DRUG

Given PO or IV

Doxorubicin

Intervention Type DRUG

Given IV

Methotrexate

Intervention Type DRUG

Given IV

Rituximab

Intervention Type BIOLOGICAL

Given IV

Vincristine

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Bortezomib

Given IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Cytarabine

Given IV

Intervention Type DRUG

Dexamethasone

Given PO or IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Methotrexate

Given IV

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Vincristine

Given IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 .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 Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone Adriablastin Hydroxyl Daunorubicin Hydroxyldaunorubicin 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 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 LEUROCRISTINE VCR Vincrystine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Confirmed diagnosis of previously untreated nodular or diffuse mantle cell lymphoma and their blastoid cytologic variant.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Serum bilirubin \< 1.5 mg/dl and serum creatinine \< 2.0 mg/dl within 14 days before enrollment (unless higher levels are due to lymphoma).
* Platelet count \> 100,000/mm\^3 within 14 days before enrollment (unless due to lymphoma).
* Absolute neutrophil count (ANC) \> 1,000/mm\^3 within 14 days before enrollment (unless due to lymphoma).
* Cardiac ejection fraction \>= 50% by echocardiogram (ECHO) or multigated acquisition (MUGA).
* Patients must be willing to receive transfusions of blood products.
* Voluntary 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.
* Female subject is either post-menopausal for at least 1 year before the Screening visit or surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of birth control, at the same time (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.
* Male subject, even if surgically sterilized (ie, status post vasectomy) agrees to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.

Exclusion Criteria

* Human immunodeficiency virus (HIV) infection.
* Central nervous system (CNS) involvement.
* Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
* Concurrent or previous malignancy with \< 90% probability of survival at 5 years.
* Patient has \>= grade 2 peripheral neuropathy within 14 days before enrollment.
* Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiography (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
* Patient has hypersensitivity to bortezomib, boron or mannitol.
* Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
* Participating in clinical trials with other investigational agents not included in this trial within 14 days of the start of this trial and throughout the duration of this trial.
* Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No