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Richter's SyndromePhase 2CHOP-ORNCT01171378

Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter's Syndrome

A Phase 2 study testing Ofatumumab in people with Richter's Syndrome, run by University of Oxford at 9 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate Ofatumumab in combination with CHOP (cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone, the standard chemotherapy treatment) in induction and maintenance treatment of Richter's Syndrome. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Richter's Syndrome
What is being tested?
Ofatumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
9 sitesUnited Kingdom
Study dates
Apr 2011to 19 Apr 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent prior to performing any study-specific procedures
  • Patients with B-CLL and newly diagnosed not previously treated and biopsy proven DLBCL Richter's transformation
  • Computerized tomography (CT) scan performed within 6 weeks prior to starting treatment.
  • ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1, 2 or 3
  • Age 18 years and over.

Who cannot join

  • CHOP or CHOP-like anthracycline containing treatment for DLBCL within 6 months prior to registration.
  • Known central nervous system (CNS) involvement of B-CLL.
  • Any malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma.
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis.
  • Subjects meeting any of the following criteria must not be enrolled in the study:
  • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg (the surface antigen of the Hepatitis-B-Virus). In addition, if negative for HBsAg but HBcAb (Hepatitis B core Antibody) positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Consent will be sought prior to any test being performed.
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  • Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • History of significant cerebrovascular disease in last 6 months.
  • Known Human immunodeficiency virus (HIV) positive.
  • Known or suspected hypersensitivity to components of investigational product.
  • Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 (start of treatment, cycle 1, day 1).
  • Current participation in any other interventional clinical study.
  • Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Breast feeding women or women with a positive pregnancy test at screening.
  • Women of childbearing potential not willing to use adequate contraception during study and for 12 months after last dose of Ofatumumab. Adequate contraception is defined as abstinence, hormonal birth control or intrauterine devices.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United Kingdom9 sites

  • Queen Elizabeth Hospital Birmingham

    Birmingham, B15 2TT

  • Royal Bournemouth Hospital

    Bournemouth, BH7 7DW

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • St James University Hospital

    Leeds, LS9 7TF

  • Royal Liverpool University Hospital

    Liverpool, L7 8XP

  • St Bartholomew's Hospital

    London, EC1A 7BE

  • Kings College Hospital

    London, SE5 9RS

  • Christie Hospital

    Manchester, M20 4BX

  • Churchill Hospital

    Oxford, OX3 7LJ

Other trials in United Kingdom

About this study

Official title: Single Arm NCRI Feasibility Study of CHOP in Combination With Ofatumumab in Induction and Maintenance for Patients With Newly Diagnosed Richter's Syndrome

The purpose of this study is to evaluate Ofatumumab in combination with CHOP (cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone, the standard chemotherapy treatment) in induction and maintenance treatment of Richter's Syndrome. This study aims to evaluate the overall response rate to CHOP-O (CHOP in combination with Ofatumumab) according to the Revised Response Criteria for Malignant Lymphoma. The hypothesis would be that treatment with CHOP-O for Richter's Syndrome (RS), shows a difference in overall survival (more people living longer), when compared with the standard treatment of CHOP-R (CHOP chemotherapy plus Rituximab).

Read the detailed description

Richter's Syndrome (RS) is a high-grade transformation that occurs in 5-15% of patients with B cell chronic lymphocytic leukaemia (B-CLL). RS is a complication of B-CLL in which the leukemia changes into a fast-growing diffuse large B cell lymphoma (DLBCL). The pathogenesis (mechanism by which the disease is caused) of RS is poorly understood and predictors of transformation and response to treatment are unknown. Management of RS remains unsatisfactory; the mean overall survival of patients treated with conventional chemo-immunotherapy such as CHOP-R is 8 months from the end of treatment.

CHOP is the acronym for a chemotherapy regimen, cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone) and the R stands for the monoclonal antibody, Rituximab. Ofatumumab, a next generation monoclonal anti CD20 antibody, has proven single agent activity in relapsed/refractory B-CLL and other non-Hodgkin lymphomas. In addition, it has shown a favourable safety profile in the maintenance setting.

Therefore, we propose to evaluate Ofatumumab in combination with CHOP in induction and maintenance treatment of patients with RS.

The primary objective of the study will be to evaluate overall response rate (ORR) to CHOP-O (CHOP chemotherapy plus Ofatumumab) according to the Revised Response Criteria for Malignant Lymphoma (Cheson).

Secondary objectives will be feasibility of recruitment, progression free survival and overall survival, the clinical benefit and changes in patient reported outcome measures, safety and tolerability.

This is a multi-centre non-randomised Phase II National Cancer Research Institute (NCRI) feasibility study in 35 patients with newly diagnosed Richter's Syndrome in the UK. CHOP-O will be given for six cycles followed by six cycles of Ofatumumab maintenance treatment every eight weeks and a three months follow-up period. The total duration of recruitment will be 24 months starting from the opening of the first site.

Being tested
Ofatumumab
Keywords
Richter's Syndrome, High-grade transformation in patients with B cell chronic lymphocytic leukemia, Feasibility, Ofatumumab Induction and maintenance, CHOP, CHOP-0, CHOP-OR, Non Hodgkin's lymphoma
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OfatumumabDrug

    Also called Arzerra

    1000mg vials (50ml @ 20mg/ml), or 100mg vials (5ml @20mg/ml), to be given as an Intravenous (IV) infusion.

    Ofatumumab will be infused intravenously on day 1 (300 mg), day 8 (1000 mg) and day 15 (1000mg) in the first cycle, followed by infusions every 3 weeks of 1000 mg on the first day of each cycle for a total of 6 cycles. Maintenance treatment will start 4 weeks after day 1 of cycle 6 in week 20 and consists of six infusions of ofatumumab every 8 weeks

Study groups in NCT01171378
Study groupRoleWhat they receive
OfatumumabOtherSingle arm study
Receives: Drug: Ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response

    Objective response as defined by the revised response criteria for malignant lymphoma (Cheson et al, JCO, Vol 25, No 5, 2007).

    Patients will be classified as responders/non-responders as follows: complete remission (CR), nodular partial remission (nPR) and partial remission (PR) are classified as responders; while stable disease (SD) and progressive disease (PD) are classified as non-responders. Non-evaluable patients will be classified as non-responders.

    Measured: Week 20

Secondary outcomes (7)

  1. Overall survival

    Overall survival where length of survival is defined in whole days as the time from entry into the study until death from any cause. For those who are not observed to die during the course of the trial will be censored at their last known follow-up date.

    Measured: 72 weeks

  2. Progression free survival

    Progression free survival where length of survival is defined in whole days as the time from entry into the study until lymphoma progression or death from any cause. For those who are not observed to progress or die during the course of the trial will be censored at their last known progression-free follow-up date

    Measured: 72 weeks

  3. Duration of response

    Duration of response defined in whole days as the time between recorded response to disease progression or death from any cause. Patients will be censored at the date of their last follow-up visit at which the response was assessed.

    Measured: 72 weeks

  4. Time to next DLBCL therapy

    Time to next DLBCL therapy defined in whole days as the time from the end of study treatment and the start of the next DLBCL therapy other than CHOP in combination with ofatumumab. Patients will be censored at the date of their last follow-up visit at which the further treatment was assessed.

    Measured: 72 weeks

  5. Reduction in Tumour Size

    Reduction in Tumour Size will be measured by the absolute value of and percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from screening to post-baseline computerised tomography (CT) scans. CT scans will be complemented by positron emission tomography (PET) scanning in patients with bulky (>5cm) lymphadenopathy from B-CLL.

    Measured: 13, 20 and 72 weeks

  6. Patient reported outcomes

    Patient reported outcomes these will be assessed using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionaire) and the EORTC QLQ-CLL16 at baseline and regular follow-up visits throughout the trial.

    Measured: Baseline, week 13, week 20, every 2 months until week 72 and at week 72.

  7. Safety

    Safety - Adverse events (AE) and abnormal clinical and laboratory findings will be collected at all follow-up visits and up to 4 weeks post end of treatment.

    Measured: Throughout trial and up to 4 weeks post end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2010 (estimated)
  2. Study startApr 2011
  3. Primary completionFeb 2015
  4. Study completion19 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01171378
Sponsor's protocol ID
OCTO_018
Other IDs
OFT113560, 2009-016459-23, 2009
Acronym
CHOP-OR
Status last verified
Apr 2018
First submitted
22 Jul 2010
Last updated
25 Apr 2018
Results posted
No
Data monitoring committee
No

Publications

  • Eyre TA, Clifford R, Roberts C, Boyle L, Francis A, Schuh A, Dutton SJ. Single arm NCRI phase II study of CHOP in combination with Ofatumumab in induction and maintenance for patients with newly diagnosed Richter's syndrome. BMC Cancer. 2015 Feb 13;15:52. doi: 10.1186/s12885-015-1048-9.

    PubMed 25775024

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ofatumumab in people with Richter's Syndrome, run by University of Oxford at 9 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response (time frame: Week 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01171378, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.

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