AL Amyloidosis, Amyloid, Refractory AL Amyloidosis
Conditions
Brief summary
This study will test the hypothesis that in patients with previous daratumumab exposure, combination therapy of daratumumab, pomalidomide, and dexamethasone (DPd) will yield higher complete remission (CR) rates in relapsed/refractory amyloidosis than historical pomalidomide/dexamethasone treatment.
Interventions
DRUGDaratumumab SC
Given as 1800mg via injection
DRUGPomalidomide
Given as 4mg oral capsule
DRUGDexamethasone
Given as 20mg or 40 mg IV and 20mg or 40mg oral tablet.
Sponsors
Weill Medical College of Cornell University
Janssen Scientific Affairs, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary AL amyloidosis of tissue * Relapsed and/or refractory AL amyloidosis * Has received daratumumab or Faspro in any prior line of therapy * Prior pomalidomide exposure allowed if ≥ PR achieved and no disease progression occurred within 60 days of last dose received * Measurable disease * Able to give voluntary written consent * Eastern Cooperative Oncology Group performance status and/or other performance status 0, 1, or 2. * Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. * Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN) (Total bilirubin ≥ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN. * eGFR ≥ 20 mL/min/1.73 m2 (as calculated by Modified Diet in Renal Disease (MDRD) formula)
Exclusion criteria
* Non-AL amyloidosis * Clinically overt myeloma * Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies. * Clinically significant cardiac disease * Severe obstructive airway disease * Female patients who are lactating or have a positive serum pregnancy test during the screening period * Planned high-dose chemotherapy and autologous stem cell transplantation within 6, 28-day treatment cycles after starting on treatment. * Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy. * Major surgery within 14 days before enrollment. * Radiotherapy within 14 days before enrollment. * Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before study enrollment. Systemic treatment, within 14 days before the first dose, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, see Appendix 11.7), or use of Ginkgo biloba or St. John's wort. * Positive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C * Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Complete Hematologic Response | Follow-up for up to 1 year | Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Very Good Partial Response (VGPR) or better hematologic response rates | Follow-up for up to 5 years | Duration of hematologic VGPR or better response is defined as the time between the date of initial documentation of hematologic VGPR or better response to the date of first documented evidence of hematologic progressive disease. |
| Low-dFLC Partial Response Rate (applicable to low-dFLC pt group) | Follow-up for up to 1 year | Percentage of participants who achieve a low-dFLC partial hematologic response rate and met criteria at screening for low-dFLC response assessment |
| Percentage of participants with an Organ Response | Follow-up for up to 3 years | Organ response rate (OrRR) for kidney and cardiac is defined as the proportion of baseline organ involved participants who achieve organ response in each corresponding organ. Organ response defined for cardiac: N-terminal brain pronatriuretic peptide (NT-proBNP) response (\> 30% and \> 300 nanogram per liter \[ng/L\] decrease in participants with baseline NT-proBNP \>= 650 ng/L) or New York Heart Association (NYHA) class response (\>= 2 class decrease in participants with baseline NYHA class 3 or 4); for kidney: decrease in proteinuria by \>=30% or below 0.5 grams /24 hours without renal progression. |
| Median estimate of months that participants have Progression Free Survival | Follow-up for up to 5 years | Median estimate calculated using the Kaplan-Meier methodology |
| Median number of months of participant's Overall Survival | Follow-up for up to 5 years | Overall survival (OS) is measured from the date of enrollment to the date of the participant's death |
| Time to Complete Hematologic Response | Follow-up for up to 1 year | Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response. |
| Time to Hematologic Progression | Follow-up for up to 5 years | Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression |
| Time until Next Treatment Therapy | Follow-up for up to 5 years | Measured in months from the date of enrollment to the start date of subsequent treatment for AL amyloidosis |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORmateo Mejia Saldarriaga, MD
Weill Medical College of Cornell University
Outcome results
None listed