The Role of Ixazomib in Autologous Stem Cell Transplant in Relapsed Myeloma - Myeloma XII (ACCoRd)
ConditionMultiple Myeloma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Leeds
About this trial
Study design: Randomised, controlled, multi-centre, open-label, phase III trial (with a single intervention registration phase).
Primary Objectives
The primary objectives of this study are to determine:
* The impact on Depth of Response (DoR: less than VGPR versus VGPR or better) when salvage ASCT conditioning is augmented by the addition of a proteasome inhibitor * The influence of a consolidation and maintenance strategy on the Durability of Response (DuR:PFS)
Secondary objectives
The secondary objectives of this study are to determine:
* Overall survival * Time to disease progression * The overall response rate following ixazomib, thalidomide and dexamethasone (ITD) re-induction * Time to next treatment * Progression-free survival 2 (PFS2) * Duration of response * Minimal Residual Disease (MRD) negative rate post re-induction, post-ASCT and conversion after ITD consolidation * Engraftment kinetics * Toxicity and safety * Quality of life (QoL)
Participant population (refer to protocol section 9 for a full list of eligibility criteria).
* Relapsed MM (with measurable disease by IMWG criteria) previously treated with ASCT * First progressive disease (PD) at least 12 months since first ASCT, requiring therapy. * ECOG Performance Status 0-2 * Aged at least 18 years * Adequate full blood count and renal, hepatobiliary, pulmonary and cardiac function * Written informed consent
Interventions: All participants will be registered at trial entry and will receive re-induction therapy with 4-6, 28-day cycles of ixazomib, thalidomide and dexamethasone (ITD), in order to reach maximum response. Participants who achieve at least stable disease (SD) will be randomised on a 1:1 basis to receive either conventional ASCT (ASCTCon), using melphalan, or augmented ASCT (ASCTAug), using melphalan with ixazomib. All participants achieving or maintaining a minimal response (MR) or better following trial ASCT will undergo a second randomisation to consolidation and maintenance or no further treatment. Participants randomised to consolidation and maintenance will receive treatment as follows: consolidation with 2 cycles of ITD and maintenance with ixazomib until disease progression.
Number of participants: 406 participants will be registered into the trial to allow 284 participants to be randomised at the first randomisation (R1) and 248 participants to be randomised at the second randomisation (R2).
Eligibility criteria
Qualifiers
Diagnosed with relapsed MM (with measurable disease, according to IMWG criteria (Appendix 2)) previously treated with ASCT).
First Progressive Disease (PD) at least 12 months following first ASCT, requiring therapy.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (Appendix 3).
Aged at least 18 years.
Disqualifiers
Received prior second line therapy for their relapsed disease other than local radiotherapy, therapeutic plasma exchange, or dexamethasone (up to a maximum of 200mg is allowed but not within 30 days prior to registration). Radiotherapy sufficient to alleviate or control pain of local invasion is permitted, but must not be within 14 days before registration. Patients who have received hemi-body radiation or similar since relapse will not be eligible.
≥Grade 2 peripheral neuropathy within 14 days before registration.
Known HIV seropositivity.
Known resistance, intolerance or sensitivity to any component of the planned therapies.
Trial design
Treatments tested in this trial
- Ixazomib, thalidomide, & dexamethasone (ITD) re-induction
- Conventional autologous stem cell transplant (ASCT-con)
- Augmented autologous stem cell transplant (ASCT-aug)
- ITD consolidation and ixazomib maintenance vs. No further therapy
Treatment groups
406 Participants
are divided into 2 treatment groupsSponsors and collaborators
Source ClinicalTrials.gov