Clinical trial NCT00513955: Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Official title: A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent mantle cell lymphoma
Lead sponsor: University Hospital Plymouth NHS Trust
Sponsor class: OTHER
First posted: 2007-08-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Disease progression
timeFrame: 30 days and every 12 weeks
measure: Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
timeFrame: continual after first drug dose
Secondary outcomes:
Other outcomes:
Locations:
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital
state: England
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Mid Kent Oncology Centre at Maidstone Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: England
city: Norfolk
country: United Kingdom
facility: James Paget Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Prescot Merseyside
country: United Kingdom
facility: Whiston Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: England
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Llanelli
country: United Kingdom
facility: Prince Philip Hospital
state: Wales
Study officials:
affiliation: Derriford Hospital
name: Simon Rule, MD
role: STUDY_CHAIR
References:
citation: 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.