None listed
Conditions
Brief summary
Multiple myeloma is a plasma cell malignancy that remains incurable. In multiple myeloma, patients with non-measurable disease, poor kidney function, extramedullary relapse, or Central nervous system myeloma are frequently excluded from clinical trials. Considering this, none of the available treatments have been adequately studied in these populations, and these patients represent a group with an unmet clinical need. We plan to establish a platform trial to look at these orphan groups (strata) of patients who have previously had no prospect of enrolment in clinical trials and in groups of patients who have not been explored before. Therefore, this clinical trial aims to assess the effectiveness of different treatment regimens for patients with first or second relapse of Multiple Myeloma. Who is it for? You may be eligible for this study if you are aged 18 or older, you have been diagnosed with Multiple myeloma and have had 1-2 prior lines of treatment. Study details Participants who choose to participate in this trial will undergo screening assessments to see if they meet one of the four following disease criterions described as stratums: •Stratum A: Poor kidney function, defined by a laboratory value of creatinine clearance (CrCl) less than 30mls per minute. •Stratum B: Non-measurable disease (defined by specific levels for blood and urine tests collected at screening) •Stratum C: presence of a plasma cell tumour that develops outside the bone marrow (extramedullary plasmacytoma) •Stratum D: Central Nervous System (CNS) myeloma Once the participant has met one of the four disease criteria described above, they will be assigned to the corresponding platform clinical trial (called appendixes) based of the four stratums described above. Once it is determined which platform trial they should be assigned to, the participant will be screened and consented again for the platform trial and go on to receive treatment if they meet the eligibility for the specific platform trial. This will continue until the participant experiences either unacceptable toxicity, or disease progression. Participants will be monitored for adverse effects for the duration of treatment, as well as the start of every cycle for assessment of their response to treatment through blood and urine samples and/or bone marrow biopsies, and assessment of quality of life through completion of a questionnaire. It is hoped this research will determine whether the combination of different treatments in treating a specific population of participants with relapsed or refractory myeloma is successful. If this combination treatment is found to be effective, it may be used to improve the health outcomes of future patients with refractory and relapsed multiple myeloma.
Interventions
This trial will be a platform trial evaluating patients with relapsed/refractory
(R/R) multiple myeloma with different drug combinations in different patient
strata:
Stratum A: Renal impairment (Creatinine Clearance less than 30ml/min)
Stratum B: Non-measurable disease
Stratum C: Extramedullary plasmacytomas
Stratum D: Central Nervous System involvement
Procedures for relevant treatment domains will be found in the relevant appendix to this master protocol. The participants will complete the
This trial will be a platform trial evaluating patients with relapsed/refractory (R/R) multiple myeloma with different drug combinations in different patient strata: Stratum A: Renal impairment (Creatinine Clearance less than 30ml/min) Stratum B: Non-measurable disease Stratum C: Extramedullary plasmacytomas Stratum D: Central Nervous System involvement Procedures for relevant treatment domains will be found in the relevant appendix to this master protocol. The participants will complete the following activities prior to being allocated to a specific treatment domain: 1. Participant diagnosed with relapsed/refractory multiple myeloma. 2. Participant will sign a master screening consent form and entered into a database and registered. Participants will be screened prior to being allocated to a stratum. Participants will undergo undergo blood, urine, CT (Neck/chest/abdomen/pelvis), CT skeletal survey, PET and MRI Brain prior to entering the study to ensure all eligibility criteria are met. 3.Strata allocation (trial registration number allocated) based on the abovementioned stratums A to D. 4. Once Strata allocation identified, participant will be consented to available treatment domain 5. Participant will be undergo screening procedures for that specific domain study. 6.Treatment domain allocated to participant. Therapies within the domain studies will consist of a combination of chemotherapy and targeted biological therapies. Treatment domains may involve a single treatment, or multiple treatments to be trialled. For those domains with multiple treatments, participants may be randomised to one of the available treatments once they have been allocated to that domain. Duration of this platform trial will depend on the treatment domain (eg. Total trial duration for domain 1 is three years). There is no minimum or maximum number of cycles of treatment and study treatment will continue until the participant experiences either unacceptable toxicity, or disease progression.
Sponsors
Australasian Leukaemia & Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All of the following criteria must be satisfied for enrolment in the trial. The domain specific appendix can refine the inclusion and exclusion criteria in this Master Protocol. 1. Histologically confirmed diagnosis of symptomatic multiple myeloma as per IMWG 2. Relapsed or refractory multiple myeloma with documented evidence of progressive disease (PD) following at least 1 prior line of therapy 3 .Must met one of the following criteria • Renal impairment, defined as Cockcroft-Gault, CrCl less than 30ml/min (stratum A) • Non-measurable disease, defined as a paraprotein less than 5g/L on serum EPG/IFE, involved light chain less than 100mg/L and urinary Bence Jones protein less than 200mg/L (stratum B) • Extramedullary plasmacytoma (stratum C) • CNS myeloma (stratum D) 4. Has provided written informed consent 5. Available for follow-up for 3 years 6 .Females of childbearing potential must use an effective method of contraception or practice absolute abstinence as required for individual drug combinations (see relevant appendices) 7. Male patients must use contraception measures as required for individual drug combinations (see relevant appendices) 8 .For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 9. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. 10. An ECOG performance status score of 2 or less at Screening 11. Subjects must agree not to share their medication and to return unused supplies
Exclusion criteria
Presence of any of the following criteria will exclude the subject from enrolment in the trial. The domain specific appendix can refine the inclusion and exclusion criteria in this Master Protocol. 1. Women who are pregnant or lactating. 2. Patients who have had investigational anti-cancer therapy, chemotherapy or radiotherapy within 4 weeks of Cycle 1 Day 1 3. Prior diagnosis of cancer that was: • more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% • within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix 4. Documented systemic amyloid light chain amyloidosis 5. Red blood cell or platelet transfusion within 14 days of screening 6. Patients with uncontrolled intercurrent illness, e.g. uncontrolled active hypertension or diabetes. 7. Active, unstable cardiovascular function: a. Symptomatic ischemia b. Uncontrolled, clinically-significant conduction abnormalities (patients with ventricular tachycardia on antiarrhythmics are excluded, patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded) or c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class greater than or equal to 3, or d. Myocardial infarction (MI) within 3 months prior to C1D1 e. Ejection fraction (EF) less than 50% at screening 8. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable. 9. Known HIV infection 10. Patients with psychiatric illness/social situations that would limit compliance with trial requirements. 11. Has any other clinically important abnormalities as determined by the investigator that may interfere with participation in or compliance with the trial. 12. Presence of any psychological, familial or sociological condition potentially hampering compliance with the trial protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Outcome results
None listed