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| ID | Type | Description | Link |
|---|---|---|---|
| 1452862 | Other Grant/Funding Number | StandUp2Cancer (in collaboration with Janssen) |
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| Name | Class |
|---|---|
| Janssen Pharmaceuticals | INDUSTRY |
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The purpose of this study is to investigate whether teclistamab-daratumumab combination is effective and safe in AL amyloidosis.
The study treatment is divided into cycles (C) and each cycle is 28 days (D). Study treatment is expected to last 6 months.
The purpose of this study is to assess the effectiveness and safety of teclistamab-daratumumab combination in newly diagnosed AL amyloidosis. The study aims to evaluate whether this combination is able to effectively decrease the level of toxic amyloid-producing light chains circulating in the participants' blood, with the overarching goal of avoiding organ damage, improving organ function, and prolonging life.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Teclistamab-Daratumumab | Experimental | All participants in this study will receive teclistamab and daratumumab. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Teclistamab | Drug | Teclistamab is a T-cell redirecting bispecific antibody (BsAb) targeting CD3 on T-cells and B-cell maturation antigen (BCMA) on plasma cells. |
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| Measure | Description | Time Frame |
|---|---|---|
| Hematologic Complete Response (Heme-CR) rate | Heme-CR will be defined as: involved free light-chain level less than the upper limit of the normal range with negative serum and urine immunofixation; normalization of the uninvolved free light-chain level or free light-chain ratio will not be required to determine a complete response. | 6 months from treatment initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Minimal Residual Disease (MRD) negativity rate by Free Light Chain Mass Spectrometry (FLC-MS) in serum | Secondary outcome is to assess the rate of minimal residual disease (MRD)-negativity and sustained MRD-negativity with Teclistamab-Daratumumab | 1 month, 3 months, 6 months, and 18 months |
| MRD-negativity rate by multiparameter flow cytometry (MFC) in bone marrow |
| Measure | Description | Time Frame |
|---|---|---|
| Hematologic event-free survival (Heme-EFS) | Heme-EFS will be calculated as a time-to-event endpoint using Kaplan-Meier method. | Throughout Cycle 2 and Cycle 6 (each cycle is 28 days) on Day 1; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months from treatment initiation) |
Inclusion Criteria:
Age >18 years and able to sign Informed Consent Form (ICF). If the individual being considered for participation in this study is unable to provide informed consent due to medical, cognitive, or other conditions, a legally authorized representative (LAR) may consent on their behalf.
Ability to comply with the study protocol, in the investigator's judgment.
Confirmed histopathological diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) or Immunofluorescence (IF) on a tissue biopsy that is positive for Congo Red.
Patient must not have received any prior plasma cell clone-directed therapy.
Measurable hematologic disease, defined as one of the following:
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
One or more organs involved by AL amyloidosis as per consensus guidelines
Pre-treatment clinical laboratory values meeting the following criteria during the screening phase:
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs.
For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
Exclusion Criteria:
Prior therapy for AL amyloidosis or multiple myeloma with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to C1D0.
Patients meeting criteria for symptomatic multiple myeloma by any one of the following: (a) Lytic lesions on imaging (Skeletal survey, whole body CT or MRI, or PET/CT) (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, (d) Bone marrow plasma cell infiltrate of greater than 60%.
Patients with involved/uninvolved serum FLC ratio>100 as the sole myeloma-defining event will be allowed.
Evidence of significant cardiovascular conditions as specified below:
History of other malignancy that could affect compliance with the protocol or interpretation of results.
Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
Patients on renal replacement therapy
Patients with HIV who are not on HAART or those with active hepatitis A, B, or C infection.
Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted, as per investigators' discretion.
Known hypersensitivity to any of the agents
Patients who are receiving any other investigational agent concurrently.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Central Nurse Navigator, RN | Contact | (212) 342 5162 | cancerclinicaltrials@cumc.columbia.edu |
| Name | Affiliation | Role |
|---|---|---|
| Suzanne Lentzsch, MD, PhD | Columbia University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Irving Medical Center | Recruiting | New York | New York | 10032 | United States |
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| ID | Term |
|---|---|
| D000075363 | Immunoglobulin Light-chain Amyloidosis |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000686 | Amyloidosis |
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| ID | Term |
|---|---|
| C556306 | daratumumab |
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| Daratumumab and Hyaluronidase-fihj | Drug | Daratumumab is an monoclonal antibody that targets the CD38 protein on the surface of myeloma cells. |
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The MRD-negativity rate by 6 and 18 months will be reported descriptively. |
| 6 months and 18 months |
| Time to heme-CR | Time to heme-CR will be calculated from the day of treatment initiation (C1D0), and will be reported as median (range). | Day 1 of each cycle, and every 6 weeks after treatment cessation (up to 1 year) |
| Major organ deterioration-progression-free survival (MOD-PFS) rate | MOD-PFS will be calculated as a time-to-event endpoint using Kaplan-Meier method. | From Cycle 2 to Cycle 6 Day 1 (Each cycle is 28 days), End of treatment visit (up to 6 months from treatment initiation), and up to 18 months from treatment initiation |
| Overall survival rate | Overall survival frequency from initiation of study drug, including cause of death for patients who die on study | Through study completion, up to 18 months from treatment initiation |
| Frequency of Cytokine Release Syndrome (CRS) | Frequency of CRS (all-grade and grade ≥3) events | Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months) |
| Rate of infections | Frequency rate of infections (all-grade and grade ≥3) will be reported descriptively. | Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months) |
| Number of participants with a heart response after treatment | Heart response is defined as N-terminal pro Brain Natriuretic Peptide (NT-ProBNP) response (>30% and >300 ng/l decrease in subjects with baseline NT-proBNP>650 ng/l) or New York Heart Association (NYHA) class response (>2 class decrease in subjects with baseline NYHA class 3 or 4) | 6 months and 18 months |
| Number of No Responses in the heart after treatment | No response in the heart is defined as ≤30% reduction in NT-proBNP from baseline | 6 months and 18 months |
| Number of Partial Responses (PR) in participants who experienced a heart response after treatment | Partial Response in the heart is defined as 31-60% reduction in NT-proBNP from baseline. | 6 months and 18 months |
| Number of Very Good Partial Responses (VGPR) in participants who experienced a heart response after treatment | VGPR in the heart is defined as >60% reduction in NT-proBNP from baseline to a nadir of >350 ng/L | 6 months and 18 months |
| Number of Complete Response (CR) in participants who experienced a heart response after treatment | Complete Response in the heart is defined as Nadir NT-proBNP≤350 ng/L | 6 months and 18 months |
| Number of participants with heart progression after treatment | Heart progression is defined as NT-proBNP progression (>30% and >300 ng/l increase) or cardiac troponin progression (>33% increase) or ejection fraction progression (>10% decrease). Subjects with progressive worsening renal function cannot be scored for NT-proBNP progression. | 6 months and 18 months |
| Number of participants with a kidney response after treatment | Kidney response is defined as 50% decrease (at least 0.5 g/day) of 24-h urine protein (urine protein must be >0.5g/day pretreatment). Creatinine and creatinine clearance must not worsen by 25% over baseline. | 6 months and 18 months |
| Number of No Responses in the kidneys after treatment | No response in the kidneys is defined as ≤30% reduction in proteinuria from baseline | 6 months and 18 months |
| Number of Partial Responses (PR) in participants who experienced a kidney response after treatment | Partial Response in the kidneys is defined as 31-60% reduction in proteinuria from baseline | 6 months and 18 months |
| Number of Very Good Partial Responses (VGPR) in participants who experienced a kidney response after treatment | VGPR in the kidneys is defined as >60% reduction in proteinuria from baseline level to a nadir level >200 mg/24 hours | 6 months and 18 months |
| Number of Complete Response (CR) in participants who experienced a kidney response after treatment | Complete Response in the kidneys is defined as Nadir proteinuria ≤200 mg/24 hours | 6 months and 18 months |
| Number of participants with kidney progression after treatment | Kidney progression is defined as 50% increase (at least 1 g/day) of 24-h urine protein to >1 g/day or 25% worsening of serum creatinine or creatinine clearance. | 6 months and 18 months |
| Number of participants with liver response after treatment | Liver response is defined as 50% decrease in abnormal alkaline phosphatase value. | 6 months and 18 months |
| Number of No Responses in the liver after treatment | No response in the liver is defined as ≤30% reduction in alkaline phosphatase (ALP) from baseline. | 6 months and 18 months |
| Number of Partial Responses (PR) in participants who experienced liver response after treatment | Partial Response in the liver is defined as 31-60% reduction in ALP from baseline. | 6 months and 18 months |
| Number of Very Good Partial Responses (VGPR) in participants who experienced liver response after treatment | VGPR in the liver is defined as >60% reduction in ALP from baseline to a nadir >2x lower limit of normal (LLN) | 6 months and 18 months |
| Number of Complete Response (CR) in participants who experienced liver response after treatment | Complete Response in the liver is defined as Nadir ALP ≤2X LLN | 6 months and 18 months |
| Number of participants with liver progression after treatment | Liver progression is defined as 50% increase of ALP from nadir value | 6 months and 18 months |
| CD4 cell count |
CD4 cells will be measured in participants before and after treatment. |
| Baseline until 18 months from treatment initiation |
| CD8 cell count | CD8 cells will be measured in participants before and after treatment. | Baseline until 18 months from treatment initiation |
| CD19 cell count | CD19 cells will be measured in participants before and after treatment. | Baseline until 18 months from treatment initiation |
| IgG level | IgG titers will be measured in participants before and after treatment. | Baseline until 18 months from treatment initiation |
| IgA level | IgA titers will be measured in participants before and after treatment. | Baseline until 18 months from treatment initiation |
| IgM level | IgM titers will be measured in participants before and after treatment. | Baseline until 18 months from treatment initiation |
| D057165 |
| Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D010265 | Paraproteinemias |