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Waldenstrom MacroglobulinemiaPhase 2/3RAINBOWNCT04061512

Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia

A Phase 2/3 study testing Dexamethasone, cyclophosphamide, rituximab and Rituximab, ibrutinib in people with Waldenstrom Macroglobulinemia, run by University College, London at 25 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Waldenström's macroglobulinaemia (WM) is a rare type of slow growing lymphoma. It develops when white blood cells grow abnormally. Typically a disease of the elderly, the median age of presentation is >70 years and the current treatment for WM is unsatisfactory, with incomplete responses and inevitable recurrence. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
Dexamethasone, cyclophosphamide, rituximab and Rituximab, ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
25 sitesUnited Kingdom
Study dates
3 Feb 2020to Mar 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

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

  • Patients ≥ 18 years
  • Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
  • Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. Suggested criteria for initiating treatment include:
  • haematological suppression to Hb <10g/dl, or neutrophils <1.5x109/l or platelets <150x109/l
  • clinical evidence of hyperviscosity
  • bulky lymphadenopathy and/or bulky splenomegaly
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  • presence of B symptoms
  • No previous chemotherapy (prior plasma exchange and steroids are permissible)
  • Eastern Cooperative Oncology Group (ECOG) performance status grade 0 - 2
  • Life expectancy of greater than 6 months
  • Written informed consent
  • Willing to comply with the contraceptive requirements of the trial
  • Negative serum or urine pregnancy test for women of childbearing potential (WOCBP)

Who cannot join

  • Prior therapy for WM
  • Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
  • CNS involvement with WM
  • Autoimmune cytopenias
  • Major surgery within 4 weeks prior to randomisation
  • Clinically significant cardiac disease including the following:
Show all 34Show fewer
  • Myocardial infarction within 6 months prior to randomisation
  • Unstable angina within 3 months prior to randomisation
  • New York Heart Association class III or IV congestive heart failure
  • History of clinically significant arrhythmias (e.g. sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  • QTcF > 480 msecs based on Fredericia's formula or Bazette's formula
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
  • Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mm Hg
  • Cardiac event within 6 months of screening (e.g. coronary artery stent) requiring dual antiplatelet treatment
  • History of stroke or intracranial haemorrhage within 6 months prior to randomisation
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (direct oral anticoagulants (DOACs) allowed)
  • History of severe bleeding disorders considered not to be disease related (Haemophilia A, B or von Willebrand's disease)
  • Requires ongoing treatment with a strong CYP3A inhibitor or inducer
  • Known infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
  • Presence of hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the patient will be excluded
  • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable
  • Women who are pregnant or breastfeeding or males expecting to conceive or father children at any point from the start of treatment until the end of the "at risk period"
  • Renal failure (creatinine clearance <30 ml/min as estimated by the Cockroft-Gault equation)
  • Patients with chronic liver disease with hepatic impairment Child-Pugh class B or C
  • Known history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies.
  • Inability to swallow oral medication
  • Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (e.g. malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease)
  • Active systemic infection requiring treatment
  • Concomitant treatment with another investigational agent
  • Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the patient's safety, or put the study at risk
  • Unwilling or unable to take PCP prophylaxis (e.g. cotrimoxazole)
  • History of prior malignancy, with the exception of the following:
  • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma, superficial bladder cancer, carcinoma in situ of the cervix or breast or localized Gleason score 6 prostate cancer without current evidence of disease.

Trial locations and contacts

25 sites in 1 country. Contact the study team or a site near you to ask about taking part.

RAINBOW Trial Coordinator contact

020 7679 9711

ctc.rainbow@ucl.ac.uk

UCL CTC haematology trials team contact

020 7679 9860

25 sites in 1 country

United Kingdom25 sites, 25 recruiting

  • Royal United Hospital, Bath

    Bath

    Josephine Crowe

    Recruiting

  • The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust

    Bournemouth

    Helen McCarthy

    Recruiting

  • East Kent Hospitals University NHS Foundation Trust

    Canterbury

    Jindriska Lindsay

    Recruiting

  • University Hospital of Wales

    Cardiff

    Simona Gatto

    Recruiting

  • Colchester Hospital

    Colchester

    Gavin Campbell

    Recruiting

  • Mid Yorkshire NHS Trust

    Dewsbury

    Joanna Haughton

    Recruiting

  • Royal Devon University Hospital

    Exeter

    Paul Kerr

    Recruiting

  • Medway Maritime Hospital

    Gillingham

    Sudarshan Gurung

    Recruiting

  • Castle Hill Hospital

    Hull

    James Bailey

    Recruiting

  • NHS Lanarkshire

    Lanark

    Iain Singer

    Iain Singer

    Recruiting

  • St James's University Hospital

    Leeds

    Roger Owen

    Recruiting

  • Leicester Royal Infirmary

    Leicester

    Ben Kennedy

    Recruiting

  • Barking, Havering and Redbridge University Hospitals NHS Trust

    London

    Karan Wadehra

    Recruiting

  • Barts Health NHS Trust

    London

    Rebecca Auer

    Recruiting

  • King's College Hospital

    London

    Kirsty Cuthill

    Recruiting

  • Northwick Park Hospital

    London

    Amita Ranger

    Recruiting

  • University College London Hospitals NHS Foundation Trust

    London

    Shirley D'Sa

    Recruiting

  • Christie NHS Foundation Trust

    Manchester

    Kim Linton

    Recruiting

  • Norfolk and Norwich Hospital

    Norwich

    Angela Collins

    Recruiting

  • Oxford University Hospital

    Oxford

    Jaimal Kothari

    Recruiting

  • University Hospitals Plymouth NHS Trust

    Plymouth

    David Lewis

    Recruiting

  • Salisbury NHS Foundation Trust

    Salisbury

    James Milnthorpe

    Recruiting

  • Torbay & Newton Abbot Hospital

    Torquay

    Deborah Turner

    Recruiting

  • Royal Cornwall Hospital

    Truro

    David Tucker

    Recruiting

  • Hampshire Hospitals NHS Foundation Trust

    Winchester

    Katharine Lowndes

    Recruiting

Other trials in United Kingdom

About this study

Official title: Randomised Phase II/III Study of Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia

Waldenström's macroglobulinaemia (WM) is a rare type of slow growing lymphoma. It develops when white blood cells grow abnormally.

Typically a disease of the elderly, the median age of presentation is >70 years and the current treatment for WM is unsatisfactory, with incomplete responses and inevitable recurrence. Therefore there is a need to find alternative treatments that are more effective, leading to lasting responses and improved quality of life.

Read more

The RAINBOW study is a phase 2-3 trial assessing 'chemotherapy free' treatment as primary therapy for WM which can potentially improve response outcome, durability and importantly, reduce toxicity for WM patients. This approach will be done using the drug Ibrutinib, which in combination with rituximab (RI) will be the experimental arm. As there is no agreed standard on first-line therapy for WM, the control arm is the current treatment based on the most recently published clinical trial results. The control arm consists of rituximab, cyclophosphamide and dexamethasone (DCR), and is widely recommended by international consensus as appropriate treatment for first-line therapy for WM.

In this study, 148 adults (aged ≥ 18 years) with treatment naïve WM will be randomised on a 1:1 ratio to either the treatment or control arm.

Randomised treatment lasts for a maximum of 6 cycles and response will be assessed following 3 cycles of treatment and completion of randomised treatment at approximately 24 weeks after commencing treatment. RI patients may then have up to 5 years of Ibrutinib monotherapy.

Patients will be seen regularly during treatment and then every 3 months for 5 years after treatment discontinuation. Patients will enter annual follow up for survival until the end of trial (including progressed patients).

The study will be conducted at NHS hospitals and is expected to last 9 years and 6 months.

Being tested
Dexamethasone, cyclophosphamide, rituximab, Rituximab, ibrutinib
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • Dexamethasone, cyclophosphamide, rituximabDrug

    DRC Arm (chemotherapy) consists of dexamethasone, cyclophosphamide and rituximab treatment

  • Rituximab, ibrutinibDrug

    RI Arm (chemotherapy free) consists of rituximab and ibrutinib treatment

Study groups in NCT04061512
Study groupRoleWhat they receive
DRC ArmActive comparatorThe DRC arm (chemotherapy) is the control arm and consists of rituximab, cyclophosphamide and dexamethasone. It is widely recommended by international consensus as appropriate treatment for first-line therapy for WM.
Receives: Drug: Dexamethasone, cyclophosphamide, rituximab
RI ArmExperimentalThe RI arm (chemotherapy free) arm will be using the drug ibrutinib, which in combination with rituximab (RI) will be the experimental arm.
Receives: Drug: Rituximab, ibrutinib

What is being measured

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

  1. Percentage of patients achieving a preliminary efficacy (response) of the 'chemotherapy free' combination of rituximab and ibrutinib (RI) as primary therapy for WM.

    Measured: Overall response rate at week 24

  2. Progression free survival (PFS) analysis of rituximab/ibrutinib (RI) when compared to dexamethasone/rituximab/cyclophosphamide (DRC) at 2 years after the last randomisation

    Measured: 2 years after the last randomisation

Secondary outcomes (6)

  1. Safety and tolerability of RI compared to DRC assessed by the frequency of serious and non-serious adverse events according to CTCAE v5.0

    Measured: until 30 calendar days post last IMP administration

  2. Overall response rate (defined as complete response [CR], very good partial response [VGPR], partial response [PR] and minor response [MR]) of RI compared to DRC (at end of randomised treatment and best response over any time point)

    Measured: through study completion, an average of 2 years.

  3. Time to next treatment

    Measured: through study completion, an average of 2 years.

  4. Duration of response of RI compared to DRC

    (responding patients only)

    Measured: through study completion, an average of 2 years.

  5. Overall survival (OS) of patients treated with RI compared to DRC

    Measured: date of randomisation until the date of death (of any cause)

  6. Quality of Life:EQ-5D-5L questionnaire

    Change in quality of life (QoL) responses in each arm assessed by EQ-5D-5L questionnaire

    Measured: 1 year and 2 years after completion of randomised treatment against the baseline quality of life score

Timeline

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

  1. First posted19 Aug 2019
  2. Study start3 Feb 2020
  3. Primary completionMar 2030 (estimated)
  4. Study completionMar 2030 (estimated)

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
148 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04061512
Sponsor's protocol ID
UCL/18/0438
Acronym
RAINBOW
Status last verified
May 2024
First submitted
1 Jul 2019
Last updated
10 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Dexamethasone, cyclophosphamide, rituximab and Rituximab, ibrutinib in people with Waldenstrom Macroglobulinemia, run by University College, London at 25 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 13 inclusion and 34 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: looking for participants now, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact RAINBOW Trial Coordinator (020 7679 9711, ctc.rainbow@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients achieving a preliminary efficacy (response) of the 'chemotherapy free' combination of rituximab and ibrutinib (RI) as primary therapy for WM. (time frame: Overall response rate at week 24). The study lists 2 primary outcomes in all. 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 NCT04061512.

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 10 May 2024.

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