Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT00513955 | Completed Phase 2 DMC

• 4 other identifiers: CDR0000559820NCRN-Ply-26sEU-20747ISRCTN200600609024
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 25

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.

Conditions

Lymphoma

Keywords

recurrent mantle cell lymphoma

Outcome Measures

Primary Outcomes (2)

• Disease progression

  The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.

  30 days and every 12 weeks

• Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0

  The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.

  continual after first drug dose

Study Arms (1)

Bortezomib plus CHOP

EXPERIMENTAL

Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

Drug: bortezomib; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisolone; Drug: vincristine sulfate; Other: questionnaire administration; Procedure: quality-of-life assessment

Interventions

bortezomib DRUG

Bortezomib plus CHOP

cyclophosphamide DRUG

Bortezomib plus CHOP

doxorubicin hydrochloride DRUG

Bortezomib plus CHOP

prednisolone DRUG

Bortezomib plus CHOP

vincristine sulfate DRUG

Bortezomib plus CHOP

questionnaire administration OTHER

Bortezomib plus CHOP

quality-of-life assessment PROCEDURE

Bortezomib plus CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2
• ANC ≥ 1,000/mm³ (not related to lymphoma)
• Platelet count ≥ 30,000/mm³
• AST and ALT ≤ 3 times upper limit of normal (ULN)
• Total bilirubin ≤ 2 times ULN
• Creatinine clearance ≥ 20 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

You may not qualify if:

• Known serological positivity for HBV, HCV, or HIV
• History of allergic reaction attributable to compounds containing boron or mannitol
• Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy
• Active systemic infection requiring treatment
• Serious medical or psychiatric illness that would preclude study participation
• PRIOR CONCURRENT THERAPY:
• Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2
• Prior splenectomy or localized radiotherapy allowed
• Any prior chemotherapy regimen allowed
• Chemotherapy may have been given in combination with rituximab
• Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study
• Prior bortezomib
• Antineoplastic therapy within the past 3 weeks
• Nitrosoureas within the past 6 weeks
• Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks

Sponsors & Collaborators

• University Hospital Plymouth NHS Trust: lead

Study Sites (25)

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, RG24 9NA, United Kingdom

Location

Good Hope Hospital

Birmingham, England, B75 7RR, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, England, FY3 8NR, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Darent Valley Hospital

Dartford, England, DA2 8DA, United Kingdom

Location

Harrogate District Hospital

Harrogate, England, HG2 7SX, United Kingdom

Location

Leeds General Infirmary

Leeds, England, LS1 3EX, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

Location

Guy's Hospital

London, England, SE1 9RT, United Kingdom

Location

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

James Paget Hospital

Norfolk, England, NR31 6LA, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, England, NR4 7UY, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Whiston Hospital

Prescot Merseyside, England, L35 5DR, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, England, SR4 7TP, United Kingdom

Location

Musgrove Park Hospital

Taunton, England, TA1 5DA, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

Prince Philip Hospital

Llanelli, Wales, SA14 8QF, United Kingdom

Location

Related Publications (1)

• Furtado M, Johnson R, Kruger A, Turner D, Rule S. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. Br J Haematol. 2015 Jan;168(1):55-62. doi: 10.1111/bjh.13101. Epub 2014 Aug 22.

  PMID: 25146720 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell

Interventions

Bortezomib; Cyclophosphamide; Doxorubicin; Prednisolone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Simon Rule, MD

  Derriford Hospital

  STUDY CHAIR

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: August 8, 2007
• First Posted: August 9, 2007
• Study Start: June 1, 2006
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 5, 2014

Record last verified: 2014-11

Locations

GB (25)