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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Plymouth Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT00513955
First received: August 8, 2007
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: bortezomib
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisolone
Drug: vincristine sulfate
Other: questionnaire administration
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Plymouth Hospitals NHS Trust:

Primary Outcome Measures:
  • Disease progression [ Time Frame: 30 days and every 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0 [ Time Frame: continual after first drug dose ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 50
Study Start Date: June 2006
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib plus CHOP

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

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response).

Secondary

  • To evaluate the rates of CR and CRu.
  • To determine the median time to progression.
  • To determine the median overall survival.
  • To evaluate the toxicity and tolerability.
  • To compare the responses to these treatment regimens with those from first line therapy.
  • To compare the quality of life.

OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC.
  • Arm II (CHOP with bortezomib): 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.

In both arms, 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of mantle cell lymphoma (MCL)

    • Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction
  • Refractory to or relapsed or progressed after first line antineoplastic therapy
  • Measurable disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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:

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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
  • Radiotherapy within the past 3 weeks
  • Major surgery within the past 2 weeks
  • Concurrent investigational agents
  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: NCT00513955

Locations
United Kingdom
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, England, United Kingdom, RG24 9NA
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Good Hope Hospital
Birmingham, England, United Kingdom, B75 7RR
Blackpool Victoria Hospital
Blackpool, England, United Kingdom, FY3 8NR
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Darent Valley Hospital
Dartford, England, United Kingdom, DA2 8DA
Harrogate District Hospital
Harrogate, England, United Kingdom, HG2 7SX
Leeds General Infirmary
Leeds, England, United Kingdom, LS1 3EX
Royal Liverpool University Hospital
Liverpool, England, United Kingdom, L7 8XP
Guy's Hospital
London, England, United Kingdom, SE1 9RT
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Royal Victoria Infirmary
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
James Paget Hospital
Norfolk, England, United Kingdom, NR31 6LA
Norfolk and Norwich University Hospital
Norwich, England, United Kingdom, NR4 7UY
Derriford Hospital
Plymouth, England, United Kingdom, PL6 8DH
Whiston Hospital
Prescot Merseyside, England, United Kingdom, L35 5DR
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Sunderland Royal Hospital
Sunderland, England, United Kingdom, SR4 7TP
Musgrove Park Hospital
Taunton, England, United Kingdom, TA1 5DA
Torbay Hospital
Torquay, England, United Kingdom, TQ2 7AA
Royal Cornwall Hospital
Truro, Cornwall, England, United Kingdom, TR1 3LJ
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Raigmore Hospital
Inverness, Scotland, United Kingdom, 1V2 3UJ
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
Prince Philip Hospital
Llanelli, Wales, United Kingdom, SA14 8QF
Sponsors and Collaborators
Plymouth Hospitals NHS Trust
Investigators
Study Chair: Simon Rule, MD Derriford Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Plymouth Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT00513955     History of Changes
Other Study ID Numbers: CDR0000559820, NCRN-Ply-26s, EU-20747, ISRCTN200600609024
Study First Received: August 8, 2007
Last Updated: October 14, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Plymouth Hospitals NHS Trust:
recurrent mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on October 21, 2014