Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to see whether combination treatment of Teclistamab and Daratumumab (Tel-Dara) or combination Talquetamab and Daratumumab (Tal-Dara) will delay the onset of multiple myeloma.
Interventions
DRUGTeclistamab
Teclistamab will be administered by subcutaneous (SC) injection per discretion of treating physician. Participants will receive the recommended dosage.
DRUGTalquetamab
Talquetamab will be administered per discretion of treating physician. Participants will receive the recommended dosage.
DRUGDaratumumab SC
Daratumumab SC will be administered by subcutaneous (SC) injection per discretion of treating physician. Participants will receive the recommended dosage.
Sponsors
Carl Ola Landgren, MD, PhD
Janssen Scientific Affairs, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have histologically or cytologically confirmed smoldering multiple myeloma (SMM) based on the IMWG Criteria10 including: * Serum M-protein ≥3 g/dL and/or BMPCs≥10 % (but \<60%) * Absence of anemia: hemoglobin \>10 g/dL * Absence of renal failure: serum creatinine \<2.0 mg/dL * Absence of hypercalcemia: Calcium \<10.5 mg/dL * Absence of lytic bone lesion on X-ray, CT, or positron emission tomography (PET)/CT and not more than 1 lesion on whole body MRI (NOTE: At the discretion of the Investigator, whole body CT or PET/CT may replace MRI in patients who have a contraindication or who are unable to have MRI performed.) * Involved/uninvolved light chain ratio \<100 (unless involved light chain is ≤10 mg/dL) NOTE: Anemia, renal failure, and hypercalcemia is allowed if deemed unrelated to multiple myeloma (MM), see organ function criteria in point #5 below. 2. Patients must have measurable disease within the past 4 weeks, which is defined by any one of the following: * Serum monoclonal protein ≥ 0.5 g/dL * Urine monoclonal protein \>200 mg/24 hour * Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal kappa/lambda serum free light chain ratio (reference: 0.26-1.65) * Other measurable disease as defined by the International Myeloma Working Group (IMWG). * Because the primary endpoint is MRD negativity based on bone marrow analysis, a patient without measurable disease in blood or urine may be enrolled and assessed for MRD negativity. NOTE: In patients who received minimal prior therapy within the allowable range per
Exclusion criteria
1, patients should have had documented measurable disease within 4 weeks of starting that respective therapy if currently unmeasurable. 3. Patients age ≥18 years. 4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 assessed within the past 45 days. (See Appendix 17.1). 5. Patients must have adequate organ and marrow function ≤45 days as defined below: * Absolute neutrophil count (ANC) \>1.0 K cells/μL; At the discretion of the Investigator, patients with an ANC of 0.5 K/μL-1.0 K/μL may also be enrolled if clinically appropriate (eg, patients with a baseline neutropenia that is chronic and/or ethnic neutropenia and that does not cause complications, e.g, no history of chronic infections). * Platelet count \>75 K cells/μL * Hemoglobin \>8 g/dL (transfusions are permissible if the cause of the anemia is other than myeloma) * Total bilirubin \<1.5 X upper limit of normal (ULN). NOTE: Isolated total bilirubin ≥1.5 X ULN with conjugated \[direct\] bilirubin \<1.5 X ULN is allowed for those participants with known Gilbert's syndrome. * Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ≤2.5 X ULN * ≥30 mL/min based on Modification of Diet in Renal Disease (MDRD) 4-variable Formula calculation (Appendix 17.2) or creatine clearance (CrCl) measured by a 24-hour urine collection. The estimated glomerular filtration rate (eGFR) may also be determined by using other widely accepted methods as clinically indicated, ie, Cockcroft-Gault method or the chronic kidney disease (CKD)-epidemiology collaboration (EPI) per institutional standards. 6. Patients must have SMM that is categorized as high-risk for progression to MM-related end- organ damage by both clinical and genomic characteristics. Patients may be categorized as high risk by the Program for Study and Treatment of Malignant Hemopathies (PETHEMA) (immunoparesis and ≥95% aberrant bone marrow plasma cells (aBMPCs) by flow) and/or Mayo Clinic78 (20/2/20) criteria and/or have clonal BMPCs ≥10% with any one or more of the following criteria4: * Serum M protein ≥3 g/dL * Immunoglobulin A (IgA) SMM * Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes * Serum involved/uninvolved free light chain (FLC) ratio ≥8 (but \<100) * Progressive increase in M-protein level (evolving type of SMM; increase in serum M- protein by ≥25% on 2 successive evaluations within a 6-month period) * Clonal bone marrow plasma cells (BMPC) 50%-59% * Abnormal plasma cell (PC) immunophenotype (≥95% of BMPCs are clonal) and reduction of ≥1 uninvolved immunoglobulin isotype(s) * Chromosomal abnormalities specifically translocation of chromosomes 4 or 14 (t(4;14)) or deletion of the short arm of chromosome 17 del(17p)) or gain of the long arm of chromosome 1 (1q gain) found in ≥5% of cells * Increased circulating PCs (PCs \>5 x 106/L and/or \>5% PCs per 100 peripheral blood mononuclear cells (PBMCs) * MRI with diffuse abnormalities or 1 focal lesion, AND/OR PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction. 7. A female participant of childbearing potential must have a negative serum or urine pregnancy test at screening (at or within 45 days of study enrollment) and within 72 hours of the start of study treatment (Section 4.7) and must agree to further serum or urine pregnancy tests during the study 8. A female participant must be (as defined in Appendix 17.3): 1. Not of childbearing potential, or 2. Of childbearing potential and practicing at least 1 highly effective method of contraception (see Appendix 17.3). NOTE: Participant must agree to continue the above throughout the study and for 3 months after the last dose of study treatment. NOTE: If a woman becomes of childbearing potential after start of the study, the woman must comply with point (b) as described above. 9. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment, as anti-cancer treatments may impair fertility. 10. A female participant must agree to not breastfeed during the study and for a period of 5 months after receiving the last dose of study treatment. 11. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for a period of 3 months after receiving the last dose of study treatment. If the male participant's partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide), and the female partner of the male participant must also be practicing a highly effective method of contraception (see Appendix 17.3). NOTE: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception. 12. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment, as anti-cancer treatments may impair fertility. 13. Ability of the patient to understand and the willingness to sign a written informed consent document. 14. Have any condition that, in the opinion of the Investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements. 15. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 3.3).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD) Negative as Measured by Flow Cytometry | 12 months | MRD negative (10\^-5 sensitivity by flow cytometry) as best response by completion of 12 cycles. MRD negative result means no disease is detected after treatment. Status of MRD will be assessed using International Myeloma Working Group (IMWG) Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma, per discretion of treating physician. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Related Adverse Events | Up to 25 months | The number of treatment related serious adverse events (SAEs) and grade 3 or higher adverse events (AEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion. |
| Overall Response Rate (ORR) | Up to 24 months | Overall response rate (ORR) is determined by the number of participants achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) to protocol therapy. Response will be assessed using standard International Myeloma Working Group (IMWG) Criteria for Response in Multiple Myeloma, per physician discretion. |
| Duration of Response (DoR) | Up to 24 months | The duration of response (DoR) is measured as the time from when participants meet the criteria for stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) to protocol therapy using International Myeloma Working Group (IMWG) Criteria until the time progressive disease (PD) is documented, per discretion of treating physician. |
| Best Objective Responses (BoR) | Up to 24 months | The rate of best objective responses (BoR) is determined by the number of participants who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as their best response to protocol therapy using International Myeloma Working Group (IMWG) Criteria, per discretion of treating physician. |
| Minimal Residual Disease (MRD) Negativity Rate by Next-Generation Sequencing (NGS) | Up to 24 months | The rate of minimal residual disease (MRD) negativity by next-generation sequencing (NGS) after 24 cycles of the protocol therapy is determined by the number of participants who achieve MRD negativity by 10\^-6 sensitivity NGS, per discretion of treating physician. |
| Sustained MRD Negativity | Up to 7 years | Sustained MRD negativity is determined by the number of participants who achieve MRD negativity 1, 2, and, 4 years apart, without any positive MRD in between, per discretion of treating physician. |
| Clinical progression-free survival (clinPFS) | Up to 7 years | Clinical progression-free survival (clinPFS) is measured as the time from the participants start of protocol therapy to the clinical development of symptomatic multiple myeloma or death, per discretion of treating physician. |
| Biochemical progression-free survival (bioPFS) | Up to 7 years | Biochemical progression-free survival (bioPFS) is measured as the time from the participants start of protocol therapy to progression of multiple myeloma in the blood or death occurs, using International Myeloma Working Group (IMWG) Criteria, per discretion of treating physician. |
| Overall Survival (OS) | Up to 7 years | Overall Survival (OS) is determined by the amount of time from participants start of protocol therapy to death or to last known timepoint the participant was alive. |
| Serum Concentrations of Teclistamab and Talquetamab | Up to 7 years | Serum samples will be analyzed to determine concentrations of Teclistamab and Talquetamab using validated, specific, and sensitive methods. |
| Duration of MRD Negativity | Up to 7 years | The duration of MRD negativity is measured as the time from the first time participants achieve MRD negativity until the participant has relapsed from MRD negativity, per discretion of treating physician. |
| Pharmacokinetics of Teclistamab in multiple myeloma (MM) | Up to 7 years | Serum from venous blood samples will be collected for measurement of serum concentrations of Teclistamab (Cohort A - Teclistamab only) and the generation of Anti-drug Antibodies (ADAs) where applicable to Teclistamab per the Study Schedule. |
Countries
United States
Contacts
CONTACTMichelle Armogan
PRINCIPAL_INVESTIGATORCarl O Landgren, MD, PhD
University of Miami
Outcome results
None listed