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

Lymphoma Clinical Trial

Official title:

A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513955
• Other study ID #: CDR0000559820
• Secondary ID: NCRN-Ply-26sEU-2
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2007
• Last updated: November 4, 2014
• Start date: June 2006
• Est. completion date: October 2014

Study information

• Verified date: November 2014
• Source: Plymouth Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• bortezomib

• cyclophosphamide

• doxorubicin hydrochloride

• prednisolone

• vincristine sulfate

Other:
• questionnaire administration

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Good Hope Hospital	Birmingham	England
United Kingdom	Blackpool Victoria Hospital	Blackpool	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Darent Valley Hospital	Dartford	England
United Kingdom	Harrogate District Hospital	Harrogate	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	Leeds General Infirmary	Leeds	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Prince Philip Hospital	Llanelli	Wales
United Kingdom	Guy's Hospital	London	England
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	England
United Kingdom	Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	James Paget Hospital	Norfolk	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Whiston Hospital	Prescot Merseyside	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Musgrove Park Hospital	Taunton	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England

Sponsors (1)

Lead Sponsor	Collaborator
Plymouth Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes