Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab

AL Amyloidosis Clinical Trial

Official title:

Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04270175
• Other study ID #: 19-12021159
• Status: Recruiting
• Phase: Phase 2
• Start date: April 14, 2021
• Est. completion date: December 2028

Study information

• Verified date: July 2023
• Source: Weill Medical College of Cornell University
• Contact: Kathleen P Research Nurse Coordinator, RN
• Phone: 646-962-6500
• Email: kap9111[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: December 2028
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloid
• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis
• Refractory AL Amyloidosis

Intervention

Drug:
• Daratumumab SC
Given as 1800mg via injection
• Pomalidomide
Given as 4mg oral capsule
• Dexamethasone
Given as 20mg or 40 mg IV and 20mg or 40mg oral tablet.

Locations

Country	Name	City	State
United States	Boston University Medical Center	Boston	Massachusetts
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Weill Cornell Medicine - Multiple Myeloma Center	New York	New York
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Overall Complete Hematologic Response	Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response	Follow-up for up to 1 year
Secondary	Duration of Very Good Partial Response (VGPR) or better hematologic response rates	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.	Follow-up for up to 5 years
Secondary	Low-dFLC Partial Response Rate (applicable to low-dFLC pt group)	Percentage of participants who achieve a low-dFLC partial hematologic response rate and met criteria at screening for low-dFLC response assessment	Follow-up for up to 1 year
Secondary	Percentage of participants with an Organ Response	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.	Follow-up for up to 3 years
Secondary	Median estimate of months that participants have Progression Free Survival	Median estimate calculated using the Kaplan-Meier methodology	Follow-up for up to 5 years
Secondary	Median number of months of participant's Overall Survival	Overall survival (OS) is measured from the date of enrollment to the date of the participant's death	Follow-up for up to 5 years
Secondary	Time to Complete Hematologic Response	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.	Follow-up for up to 1 year
Secondary	Time to Hematologic Progression	Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression	Follow-up for up to 5 years
Secondary	Time until Next Treatment Therapy	Measured in months from the date of enrollment to the start date of subsequent treatment for AL amyloidosis	Follow-up for up to 5 years