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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02955810
• Date of registration: 18/10/2016
• Prospective Registration: Yes
• Primary sponsor: National University of Ireland, Galway, Ireland
• Public title: Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) With Daratumumab (DARA) CyBorD-Dara
• Scientific 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"
• Date of first enrolment: November 2016
• Target sample size: 18
• Recruitment status: Unknown status
• URL: https://clinicaltrials.gov/show/NCT02955810
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Ireland

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

=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.

Exclusion Criteria:

- 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.

- 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.

b) Patient has known moderate or severe persistent


Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Daratumumab

Drug: Bortezomib

Drug: Cyclophosphamide

Drug: Dexamethasone

Primary Outcome(s)

The rate of Complete Response (CR) post Autologous Stem Cell Transplantation (ASCT) [Time Frame: 42 months]

MTD [Time Frame: 15 months]

Secondary Outcome(s)

Complete Response Rate at the end of induction, ASCT, consolidation and maintenance [Time Frame: 42 months]

Safety and Tolerability as assessed by adverse events [Time Frame: 42 months]

Overall Survival (OS) at the end of maintenance phase [Time Frame: 42 months]

Best Overall Response [Time Frame: 42 months]

Progression Free Survival (PFS) at the end of maintenance phase [Time Frame: 42 months]

Clinical Benefit Rate (CBR) [Time Frame: 42 months]

Minimal Residual Disease (MRD) negative rate at the end of induction, ASCT, consolidation and maintenance [Time Frame: 42 months]

Secondary ID(s)

16-BCNI-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cancer Trials Ireland

Janssen Pharmaceuticals