Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: daratumumab/pomalidomide/dexamethasone Pomalidomide: (4mg orally) on days 1-21 of a 28-day cycle Dexamethasone: 20mg IV as premedication on days 1, 8, 15, and 22 20mg orally the day after daratumumab dosing for cycles 1-2 of induction 40mg IV as premedication on days 1 and 15 on daratumumab treatment days 40mg orally on non-daratumumab days (8 and 15) for cycles 3-6 20mg on day 1 of every cycle as premedication on daratumumab dosing day 1 in maintenance cycles (cycles 7 and beyond) If you are a subject age 70 and older, the dexamethasone dosing will be reduced by 50% at the time of induction. Daratumumab: 1800mg sub-cutaneously weekly x8 weeks 1800mg sub-cutaneously every 2 weeks during induction (cycles 3-6) 1800mg sub-cutaneously every 4 weeks cycles 7 and beyond |
Drug: Daratumumab
Given as 1800mg via injection
Drug: Pomalidomide
Given as 4mg oral capsule
Drug: Dexamethasone
Given as 20mg or 40 mg IV and 20mg or 40mg oral capsule.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Overall Complete Hematologic Response [Approximately 3 years]
Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response
Secondary Outcome Measures
- Median estimate of months that participants have progression free survival [Approximately 5 years]
Median estimate calculated using the Kaplan-Meier methodology
- Median number of months of participant's overall survival [Approximately 8 years]
Overall survival (OS) is measured from the date of enrollment to the date of the participant's death
- Time to Complete Hematologic Response [Approximately 3 years]
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 [Approximately 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 [Approximately 5 years]
Measured in months from the date of enrollment to the start date of subsequent treatment for AL amyloidosis
- Percentage of participants for Organ response [Approximately 5 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.
- Duration of Very Good Partial Response (VGPR) or better hematologic response rates [Approximately 3 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of primary AL amyloidosis of tissue
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Relapsed and/or refractory AL amyloidosis
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Measurable disease
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Able to give voluntary written consent
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Eastern Cooperative Oncology Group performance status and/or other performance status 0, 1, or 2.
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Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.
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Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN).
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
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Calculated creatinine clearance ≥ 30 mL/min (see Appendix 11.2).
Exclusion Criteria:
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Non-AL amyloidosis
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Clinically overt myeloma
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Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies or pomalidomide.
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Clinically significant cardiac disease
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Severe obstructive airway disease
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Female patients who are lactating or have a positive serum pregnancy test during the screening period
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Planned high-dose chemotherapy and autologous stem cell transplantation within 6, 28-day treatment cycles after starting on treatment.
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Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
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Major surgery within 14 days before enrollment.
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Radiotherapy within 14 days before enrollment.
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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.
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Positive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University | Palo Alto | California | United States | 94304 |
| 2 | Boston University Medical Center | Boston | Massachusetts | United States | 02118 |
| 3 | Weill Cornell Medicine - Multiple Myeloma Center | New York | New York | United States | 10065 |
| 4 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Janssen Scientific Affairs, LLC
Investigators
- Principal Investigator: Cara Rosenbaum, MD, Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19-12021159