Phase II study of Bortezomib, Adriamycin and Dexamethasone (PAD) therapy for previously untreated patients with multiple myeloma: Impact of minimal residual disease (MRD) in patients with deferred ASCT

ISRCTN	ISRCTN03381785
DOI	https://doi.org/10.1186/ISRCTN03381785
EudraCT/CTIS number	2010-021598-35
Secondary identifying numbers	8726

Submission date: 22/02/2011
Registration date: 22/02/2011
Last edited: 19/05/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-bortezomib-adriamycin-dexamethasone-as-first-treatment-for-myeloma-padimac

Contact information

Ms Milena Toncheva
Scientific

Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Email	padimac@ctc.ucl.ac.uk

Study information

Study design	Non-randomised interventional trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Phase II study of Bortezomib, Adriamycin and Dexamethasone (PAD) therapy for previously untreated patients with multiple myeloma: Impact of minimal residual disease (MRD) in patients with deferred ASCT (PADIMAC)
Study acronym	PADIMAC
Study objectives	The overall aim of the trial is to provide a reliable estimate of the 2-year progression-free survival (PFS) for patients who receive no further treatment after achieving a major response to induction therapy with PAD (Bortezomib, Adriamycin and Dexamethasone). Background: Multiple myeloma (MM) is a cancer of white blood cells called plasma cells. The recent incorporation of new agents with significant activity against MM (such as bortezomib) into frontline regimens has resulted in high overall and complete response rates prior to ASCT (autologous stem cell transplant). The substantial activity seen with these new drug combinations prompts an urgent re-examination of the role and timing of ASCT in MM treatment, particularly as recent data indicate that patients who have already achieved a complete response (CR) following induction therapy obtain no further benefit from ASCT. Therefore, the aim of this phase II study is to provide a reliable estimate of the PFS of patients achieving major response post-induction who receive no further treatment.
Ethics approval(s)	10/H0502/58
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Myeloma
Intervention	PAD, Patients will receive treatment to maximum response + 1 cycle, with a minimum of 4, and maximum of 6 cycles each of 21 days
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Bortezomib, adriamycin, dexamethasone
Primary outcome measure	2-year PFS for patients who, having achieved CR/VGPR following PAD therapy, do not receive any further treatment
Secondary outcome measures	Not provided at the time of registration
Overall study start date	01/11/2010
Completion date	01/04/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	Planned Sample Size: 120
Total final enrolment	153
Key inclusion criteria	1. Previously untreated patients with symptomatic myelom 2. Patients suitable for high dose therapy and ASCT 3. = 18 years of age 4. Performance score (PS) of 0-3 (ECO.G). Measurable disease as defined by one of the following: 4.1. Secretory myeloma: Monoclonal protein in the serum or monoclonal light chain in the urine (Bence Jones protein ?200mg/24hours), or serum free light chain (SFLC, involved light chain ?100mg/L provided the FLC ratio is abnormal) 4.2. Non-secretory myeloma: ? 30% plasma cells in the marrow (aspirate and/or biopsy) and at least one plasmacytoma ? 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan) 5. Adequate full blood count within 14 days before registration: 5.1. Platelet count =75x109/L 5.2. Absolute neutrophil count (ANC) =1x109/L 6. Adequate renal function within 14 days before registration: 6.1. Creatinine clearance >30ml/min 7. Adequate hepatobiliary function within 14 days before registration: 7.1. Total bilirubi<2 x upper limit of normal (ULN) 7.2. ALT/AST <2.5 x ULN 8. Adequate pulmonary function: 8.1. No evidence of a history of infiltrative pulmonary disease. If a history, then KCO/DLCO (Carbon Monoxide diffusion in the lung) =50% and/or no requirement for supplementary continuous O2 9. Adequate cardiac function: 9.1. Left ventricular ejection fraction (LVEF) =40% by echocardiogram and ECG. 10. If female and of childbearing potential (WCBP), must have a negative pregnancy test (either serum or urine HCG) 11. Able to give informed consent
Key exclusion criteria	1. Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) 2. Pregnant or breast-feeding 3. Unwilling to use adequate contraception during the study and for 6 months after the end of the study treatment womnle of childbearing potential (WCBP) or male whose partner is WCBP 4. Known history of allergy contributable to compounds containing boron or mannitol 5. Any medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patients participation in this study
Date of first enrolment	01/11/2010
Date of final enrolment	01/04/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Research UK & UCL Cancer Trials Centre, 90 Tottenham Court Road

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UK)
University/education

Institute of Child Health, Endocrinology
London
WC1N 1EH
England
United Kingdom

Website	http://www.ucl.ac.uk/ich/homepage
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Research organisation

Leukaemia and Lymphoma Research (UK)
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results		11/05/2022	No	Yes
Basic results	03/05/2021	19/05/2022	No	No
HRA research summary		28/06/2023	No	No

Editorial Notes

19/05/2022: EU Clinical Trials Register results added.
11/05/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
24/07/2020: No publications found.
06/07/2017: No publications found, verifying study status with principal investigator.