IRB Study Number 23-1012
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To compare the efficacy of elranatamab versus lenalidomide
Secondary Objectives
To compare the efficacy of elranatamab versus lenalidomide
To compare the efficacy of elranatamab versus lenalidomide
To determine the safety and tolerability of elranatamab
To evaluate the PK of Elranatamab
To evaluate the immunogenicity of elranatamab
To evaluate the impact of study intervention on participant HRQoL
Inclusion Criteria
Age and Sex:
- Participant’s age ≥18 years (or the minimum country specific age of consent if >18) at Visit 1 (Screening) or at the prescreening visit, as applicable.
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
Male participants and female participants of childbearing potential must agree to use contraception as described in Appendix 4.
Type of Participant and Disease Characteristics:
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Diagnosis of MM as defined according to IMWG criteria (Rajkumar et al, 2014a) with measurable disease at diagnosis as defined by serum M-protein ≥0.5 g/dL (5 g/L), by urine M-protein ≥200 mg/24 hours, or by serum FLC assay with involved FLC level ≥10 mg/dL, provided serum FLC ratio is abnormal.
History of 3 to 8 cycles of induction therapy for NDMM, followed by high-dose therapy and ASCT. Randomization must occur within 120 days from the stem cell transplant. For participants who receive consolidation therapy after ASCT, randomization must occur within 60 days of consolidation and within 7 months from ASCT.
PR or better according to IMWG criteria at the time of randomization.
Identification of the dominant malignant (index) clone as assessed by central laboratory NGS test (Adaptive Biotechnologies clonoSEQ® assay or as described in Appendix 10.9.6).
Must have an archived bone marrow aspirate sample(s) that identifies the dominant malignant (index) clone that is used to track MRD status by central laboratory assessment (Adaptive Biotechnologies clonoSEQ® assay [or as described in Appendix 10.9.6]). This sample should preferably be collected before induction treatment (eg, at diagnosis) or before transplant. A sample collected after transplant may be accepted with sponsor approval. If an archival sample is not available and the test result of a previous Adaptive Biotechnologies' clonoSEQ® MRD assay performed at their Seattle (WA, USA) laboratory (or as described in (Appendix 10.9.6) that identifies the index multiple myeloma clone can be retrieved for use in this study, then the result may be used with sponsor approval.
ECOG performance status ≤1.
LVEF ≥40% as determined by a MUGA scan or ECHO.
Adequate hepatic function characterized by the following:
Total bilirubin ≤2 × ULN (for Gilbert's syndrome, direct bilirubin >ULN is exclusionary);
AST ≤2.5 × ULN; and
ALT ≤2.5 × ULN.
Adequate renal function defined according to local institutional standard method: eGFR ≥30 mL/min/1.73 m2 using CKD-EPI 2021 equation (https://www.kidney.org/content/ckd-epi-creatinine-equation-2021) or estimated CrCL ≥30 mL/min using Cockcroft Gault formula. If both formulae are calculated, the higher of the 2 values may be used. A 24-hour urine collection for CrCl may also be used in equivocal cases where amyloidosis is suspected.
Adequate post-ASCT recovery of BM function at screening and randomization as characterized by the following:
ANC ≥1.0 × 109/L (use of G-CSF is permitted if completed at least 7 days prior to planned start of dosing, G-CSF should not be used to reach this level);
Platelets ≥75 × 109/L (transfusion support is permitted if completed at least 7 days prior to planned start of dosing); and
Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at least 14 days prior to planned start of dosing).
Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L).
Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
Informed Consent:
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion Criteria
Medical Conditions:
- Plasma cell leukemia defined as more than 20% circulating plasma cells and an absolute count >2 × 109/L plasma cells in peripheral blood (Rajkumar et al, 2014b)
- Amyloidosis, Waldenström’s macroglobulinemia, or POEMS syndrome.
- Known active CNS involvement or clinical signs of myelomatous meningeal involvement.
- Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment:
Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion);
Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism);
Prolonged QT syndrome or QTcF >470 msec at screening.
- Ongoing Grade ≥3 peripheral sensory or motor neuropathy.
- History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- Live attenuated vaccine within 4 weeks of the first dose.
- Known or suspected hypersensitivity to the study interventions or any of its excipients.
- Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
- Other surgical (including major surgery within 14 days prior to enrollment), medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
Prior/Concomitant Therapy:
- Previous MM maintenance treatment.
- Prior treatment with BCMA targeted therapy
Prior/Concurrent Clinical Study Experience:
- Previous administration with an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
Diagnostic Assessments:
- Positive pregnancy test (for females of childbearing potential) at any time during the study.
- Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, and known HIV or AIDS-related illness. Comments regarding specific circumstances follow.
a. COVID-19/SARS-CoV-2: This protocol excludes patients with active infections, as noted above. While SARS-CoV-2 testing is not mandated for entry into this protocol, testing should follow local clinical practice standards. If a patient has a positive test result for SARS-CoV-2 infection within 14 days prior to enrollment, is known to have asymptomatic infection or is suspected of having SARS-CoV-2, they are excluded.
b. HIV: In equivocal cases, participants whose viral load is negative may be eligible. HIV seropositive participants who are otherwise healthy and at low risk for AIDS-related outcomes could be considered eligible. Potential eligibility for a specific HIV-positive protocol candidate should be evaluated and discussed with the sponsor prior to any screening, based on current and past CD4 and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), and status of HIV treatment. Also, the potential for drug-drug interactions will be taken into consideration.
c. HBV/HCV: Relevant laboratory tests should be performed at screening. Refer to CDC website (https://www.cdc.gov/hepatitis/index.htm) for further details.
d. HBV:
This criterion excludes participants with a positive HBsAg (ie, either acute or chronic active hepatitis).
However, participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are eligible.
Patients with positive anti-HBcAb but negative HBsAg and negative anti-HBsAb profile are eligible if HBV DNA is not detected.
e. HCV:
Positive HCV antibody is indicative of infection but may not necessarily render a potential candidate ineligible, depending on clinical circumstances. Discussion with the sponsor is indicated. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In this circumstance it is recommended to test for HCV RNA. Refer to CDC website for further details (https://www.cdc.gov/hepatitis-c/hcp/diagnosis-testing/).
Other Exclusions:
- Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study, and their family members.
