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Multiple MyelomaPhase 1CyBorD-DaraNCT02955810

Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) With Daratumumab (DARA)

A Phase 1 study testing Daratumumab, Cyclophosphamide and Bortezomib in people with Multiple Myeloma, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study is a Phase Ib open label, single arm, adaptive multicentre trial. Patients with newly diagnosed Multiple Myeloma (MM) will be treated with Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) in combination with Daratumumab (DARA). Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab, Cyclophosphamide and Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteIreland
Study dates
Nov 2016to Nov 2020
Phase
Phase 1
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must sign an Informed Consent Form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
  • Patient must be between 18 and <70 years of age.
  • Patient must have documented diagnosis of multiple myeloma requiring treatment as per IMWG updated criteria for the diagnosis of multiple myeloma and measurable disease as defined by:
  • Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma
  • Measurable disease as defined by any of the following:
  • IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level
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  • ≥1.0g/dl or urine M-protein level ≥200mg/24 hours; or
  • IgA, IgE, IgD or IgM multiple myeloma: serum M-protein level ≥0.5g/dl or urine M-protein level ≥200mg/24 hours; or
  • Light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain ≥10mg/dl and abnormal serum immunoglobulin kappa lambda free light chain ratio.
  • Newly diagnosed patient eligible for high dose therapy and autologous stem cell transplantation.
  • Patient must have an ECOG performance status score of 0-2.
  • Patient must have pre-treatment clinical laboratory values meeting the following criteria during the Screening Phase:
  • Haemoglobin ≥7.5g/dl (≥5mmol/l); prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted);
  • absolute neutrophil count (ANC) ≥1.0x109/l (GCSF is permitted);
  • AST ≤ 2.5 x upper limit of normal (ULN);
  • ALT ≤ 2.5 x ULN;
  • total bilirubin ≤ 1.5 x ULN (except in patients with congenital bilirubinaemia, such as Gilbert syndrome, direct bilirubin ≤ 1.5 x ULN);
  • calculated creatinine clearance ≥40ml/min/1.73m2;
  • corrected serum calcium ≤ 14mg/dl (<3.5mmol/l); or free ionized calcium ≤6.5mg/dl (≤1.6mmol/l);
  • platelet count ≥70x109/l for patients in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50x109/l (transfusions are not permitted to achieve this minimum platelet count).
  • Patients who are women of child-bearing potential or male partners of women of childbearing potential must agree to use adequate contraception methods from signing of the informed consent form until at least 4 months after the last study drug administration.
  • Childbearing potential is defined as any woman who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally post-menopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months). The investigator or a designated associate is required to advise the patient how to achieve adequate birth control. Highly effective contraception is defined in the study as methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable), intrauterine device (IUD), intrauterine hormone -releasing system (IUS), bilateral tubal occlusion, successfully vasectomised partner and sexual abstinence. In addition, the use of condoms by patients or their partners is required unless the woman has had a hysterectomy. Contraception will start 4 weeks before the start of therapy, will continue during therapy including dose interruptions and for 4 months after the last dose of any component of the treatment regimen.
  • A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to first dose and the second within 24 hours prior to first dose.
  • Patient must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Who cannot join

  • Patient has received daratumumab or other anti-CD38 therapies previously.
  • Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein < 3g/dl; absence of criteria consistent with active/symptomatic multiple myeloma as per IMWG criteria. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment (ROTI) end organ damage.
  • Patient has a diagnosis of Waldenstrom's macroglobulinemia or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
  • Patient has prior or current systemic therapy or stem cell transplantation for any plasma cell dyscrasia, with the exception of an emergency use of a short course (equivalent of dexamethasone 40mg/day for a maximum 4 days) of corticosteroids before treatment.
  • Patient has peripheral neuropathy or neuropathy grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
  • Patient has had any prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of screening period except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate adenocarcinoma diagnosed ≥3 years and without evidence of biochemical failure, or other cancer for which the patient has undergone potentially curative therapy and has no evidence of that disease for ≥10 years.
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  • Patient has had radiation therapy within 14 days prior to start of study treatment.
  • Patient has had plasmapheresis within 28 days of registration.
  • Patient is exhibiting clinical signs of meningeal involvement of multiple myeloma.
  • 10. a) Patient has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and patients must be excluded if FEV1 < 50% of predicted normal.
  • Patient has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification. (Note that patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
  • Patient is known to be seropositive for or active human immunodeficiency virus (HIV) or known to have active hepatitis B or hepatitis C.
  • Patient has any concurrent medical or psychiatric condition or disease (e.g. active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
  • Patient has clinically significant cardiac disease, including:
  • myocardial infarction within 1 year before registration, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e. g. unstable angina, congestive heart failure, New York Heart Association Class IIIIV), OR
  • cardiac arrhythmia (NCI-CTCAE Version 4.0 Grade ≥ 2) or clinically significant ECG abnormalities, and
  • screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
  • Patient has known allergies, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the DARA Investigator's Brochure), or known sensitivity to mammalian-derived products.
  • Patient has plasma cell leukaemia (according to WHO criterion: ≥20% of cells in the peripheral blood with an absolute plasma cell count of more than 2x109/l) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Patient is known or suspected of not being able to comply with the study protocol (e.g. because of alcoholism, drug dependency, or psychological disorder). Patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
  • Patient is a woman who is pregnant, or breast-feeding, or planning to become pregnant while participating in this study or within 4 months after the last dose of any component of the treatment regimen. Or, patient is a man who plans to father a child while included in this study or within 4 months after the last dose of any component of the treatment regimen.
  • Patient has had major surgery within 2 weeks before registration or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study. Kyphoplasty is not considered major surgery.
  • Patient has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before registration or is currently enrolled in an interventional investigational study.
  • Patient has contraindication to the use of any components of the treatment regimen, per the Summary of Product Characteristics.
  • Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.

Trial locations and contacts

1 site in 1 country.

Ireland1 site

  • Galway University Hospital

    Galway

Other trials in Ireland

About this study

Official title: Phase Ib Study of Weekly Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) With Daratumumab (DARA) in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma (MM): "The CyBorD-DARA Study"

This study is a Phase Ib open label, single arm, adaptive multicentre trial. Patients with newly diagnosed Multiple Myeloma (MM) will be treated with Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) in combination with Daratumumab (DARA).

The safety profile of daratumumab to date, which does not appear to overlap with those known for approved agents, combined with its distinct MoA, suggest that the therapeutic profile of daratumumab combined with various backbone regimens may improve the treatment effect of these regimens. Additionally, daratumumab as a single agent may prolong the progression free interval for these patients. Based on the potential for cyclophosphamide to enhance ADCP, there is a strong rationale to combine DARA with a cyclophosphamide, bortezomib containing regimen. This will be the first clinical trial to explore the feasibility of combining daratumumab with a cyclophosphamide containing backbone induction regimen and if successful will provide the rationale for larger studies exploring the efficacy of this combination in greater detail.

Read the detailed description

The study will consist of 2 phases:

  • The Screening Phase will extend up to 28 days prior to Cycle 1, Day 1.
  • The Treatment Phase will be conducted in 2 parts and will extend from Cycle 1 Day 1 until treatment discontinuation.

Treatment Phase, Part 1: Induction/Transplantation/Consolidation Phase. The consolidation phase of treatment will begin approximately 30-60 days after Autologous Stem Cell Transplantation (ASCT), when the patient has recovered sufficiently and engraftment is complete.

Treatment Phase, Part 2: Maintenance Phase treatment until a maximum duration of 2 years, documented disease progression, death, loss to follow-up, or withdrawal of consent, whichever occurs first.

Keywords
Newly Diagnosed, Treatment Naiive
Medical subject headings
Multiple Myeloma

What participants receive

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

Study groups in NCT02955810
Study groupRoleWhat they receive
CyBorD-DARAExperimentalNot described
Receives: Drug: Daratumumab; Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

What is being measured

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

  1. MTD

    To determine the Maximum Tolerated Dose (MTD) for cyclophosphamide and bortezomib that can be safely administered with DARA.

    Measured: 15 months

  2. The rate of Complete Response (CR) post Autologous Stem Cell Transplantation (ASCT)

    Efficacy assessed by the rate of Complete Response (CR) post Autologous Stem Cell Transplantation (ASCT)

    Measured: 42 months

Secondary outcomes (7)

  1. Safety and Tolerability as assessed by adverse events

    Safety and Tolerability will be assessed by standard clinical and laboratory tests. Adverse event grades will be determined by the NCI CTCAE v4.03

    Measured: 42 months

  2. Complete Response Rate at the end of induction, ASCT, consolidation and maintenance

    Measured: 42 months

  3. Best Overall Response

    Measured: 42 months

  4. Minimal Residual Disease (MRD) negative rate at the end of induction, ASCT, consolidation and maintenance

    Measured: 42 months

  5. Progression Free Survival (PFS) at the end of maintenance phase

    Measured: 42 months

  6. Overall Survival (OS) at the end of maintenance phase

    Measured: 42 months

  7. Clinical Benefit Rate (CBR)

    Measured: 42 months

Timeline

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

  1. First posted4 Nov 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionSep 2018 (estimated)
  4. Study completionNov 2020 (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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02955810
Sponsor's protocol ID
16-BCNI-001
Acronym
CyBorD-Dara
Status last verified
Mar 2018
First submitted
18 Oct 2016
Last updated
29 Mar 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • O'Dwyer M, Henderson R, Naicker SD, Cahill MR, Murphy P, Mykytiv V, Quinn J, McEllistrim C, Krawczyk J, Walsh J, Lenihan E, Kenny T, Hernando A, Hirakata G, Parker I, Kinsella E, Gannon G, Natoni A, Lynch K, Ryan AE. CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study. Blood Adv. 2019 Jun 25;3(12):1815-1825. doi: 10.1182/bloodadvances.2019000010.

    PubMed 31201169

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daratumumab, Cyclophosphamide and Bortezomib in people with Multiple Myeloma, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.

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 24 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 29 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Ireland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Results are not available in the source record.

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?

MTD (time frame: 15 months). 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 NCT02955810, 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 29 Mar 2018.

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