None listed
Conditions
Brief summary
The purpose of this study is to assess whether a new combination of therapies, with stem cell transplant, will prolong remission and hold off recurrence of myeloma in patients who have been diagnosed with multiple myeloma and have not responded to standard treatment (currently Bortezomib). Who is it for? You may be eligible for this study if you are an adult who has been diagnosed with multiple myeloma and have had a minimal or no response to bortezomib based induction therapy. Study details If participants consent to take part in this study, they will receive the following: - Four cycles of daratumumab, lenalidomide and dexamethasone. These medications will be used to alter the immune system response to myeloma cells. - A transplant of their own, non-cancerous cells. - This will be followed 12 cycles of the same medications given initially (daratumumab, lenalidomide and dexamethasone) to ‘consolidate’ treatment. - After the completion of the 12 cycles, all participant will commence ‘maintenance’ phase of this study while involves daily doses of lenalidomide. Patients will also undergo routine blood assessments as per standard of care It is hoped that this treatment will provide an alternative treatment to those who have been diagnosed with multiple myeloma and have not responded to standard treatment.
Interventions
SALVAGE: Daratumumab will be given intravenously at a dose of 16mg/kg on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 and 2, and on days 1 and 15 of each 28-day cycle for cycles 3 and 4. Lenalidomide orally at a dose of 25mg once daily will be given on days 1-21 of each 28-day cycle for cycles 1 to 4. Dexamethasone at a dose of 40mg will be given on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 to 4.
After completing 3 cycles, patients will undergo a G-CSF mobilised periphe
SALVAGE: Daratumumab will be given intravenously at a dose of 16mg/kg on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 and 2, and on days 1 and 15 of each 28-day cycle for cycles 3 and 4. Lenalidomide orally at a dose of 25mg once daily will be given on days 1-21 of each 28-day cycle for cycles 1 to 4. Dexamethasone at a dose of 40mg will be given on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 to 4. After completing 3 cycles, patients will undergo a G-CSF mobilised peripheral blood stem cell (PBSC) collection. Following collection, patients will commence cycle 4 and undergo full disease re-evaluation after completion of study treatment. Autologous Stem Cell Transplant(ASCT): Within 4 to 6 weeks of completion of cycle 4 all patients with greater than or equal to 2 million/kg CD34 cells available will undergo a melphalan 200mg/m2 conditioned ASCT as per standard institutional practice. CONSOLIDATION: Commencing at between day 100 and 120 post-stem cell transplant patients without evidence of disease progression will commence consolidation. Consolidation cycles 1 to 12 will each be of 28 days duration. In consolidation cycles 1 and 2 patients will receive Daratumumab intravenously at a dose of 16mg/kg on days 1 and 15 and then on day 1 of each of cycles 3 to 12. Lenalidomide orally will be given at a dose of 25mg once daily on days 1-21 of cycles 1 and 2 and at a dose of 10mg once daily on days 1-28 of cycles 3 to 12. Dexamethasone at a dose of 40mg will be given on days 1, 8, 15 and 22 for cycles 1 to 12. MAINTENANCE: After the completion of 12 cycles of consolidation patients will commence maintenance with Lenalidomide orally 10mg once daily (after 3 months increase to 15 mg/day if tolerated) until disease progression, unacceptable toxicity of the withdrawal of consent, for a maximum of 2 years treatment.
Sponsors
Australiasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and Female patients, greater than or equal to 18 years of age. 2. Symptomatic NDMM as per IMWG criteria 3. Eligible for high-dose melphalan conditioned ASCT. 4. Patients who have had a sub-optimal response to a bortezomib-based induction therapy, where a sub-optimal response is defined as: The failure to achieve at least a minimal response (MR) with a minimum of 2 cycles of a prior bortezomib-based induction therapy OR a partial response (PR) with 4 cycles of a prior bortezomib-based induction therapy OR are bortezomib refractory, that is, have progressed while on bortezomib therapy or within 60 days of receiving their last dose of bortezomib. 5. No contraindication to the use of any of the study drugs. 6. Adequate liver function (total bilirubin less than 2.0x ULN, ALT less than 5.0x ULN) unless considered secondary to MM. 7. Absolute neutrophil count greater than or equal to 1.0 x 109/L. 8. Platelet count greater than or equal to 50 x 109/L (greater than or equal to 30 x 109/L if MM involvement in the marrow is greater than 50%), patients should not have received platelet transfusions within 7 days of the screening platelet count. 9. Hb greater than or equal to 80g/L, red cell transfusions as per institutional protocol are allowed.
Exclusion criteria
1. Patients who have had myocardial infarction within 6 months prior to enrolment, or NYHA (New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 2. Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators opinion, potentially interfere with the completion of treatment according to this protocol. 3. Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency (HIV) positivity. 4. Subject has significant airways disease according to the following definitions: a. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal. b. Subject has had known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study). 5. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening. 6. Any patient who is unable or unwilling to meet the requirements of the lenalidomide pregnancy prevention program. 7. Active malignancy with the exception of any of the following: a. Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer. b. Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for greater than 2 years. c. Stage 1 prostate cancer that does not require treatment. d. Any other cancer from which the subject has been disease-free for greater than 2 years. 8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial. 9. Participation in other clinical trials for the treatment of multiple myeloma, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
Outcome results
None listed