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

• ClinicalTrials.gov Identifier: NCT04270175
• Recruitment Status: Recruiting
• First Posted: February 17, 2020
• Last Update Posted: June 9, 2022
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Janssen Scientific Affairs, LLC
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Tracking Information

• First Submitted Date: February 12, 2020
• First Posted Date: February 17, 2020
• Last Update Posted Date: June 9, 2022
• Actual Study Start Date: April 14, 2021
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2020)

Percentage of Participants With Overall Complete Hematologic Response [ Time Frame: Approximately 3 years ]

Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 12, 2020)

• Median estimate of months that participants have progression free survival [ Time Frame: Approximately 5 years ]
  Median estimate calculated using the Kaplan-Meier methodology
• Median number of months of participant's overall survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab
• Official Title: Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Amyloid
• AL Amyloidosis
• Refractory AL Amyloidosis

Intervention

• 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.

Study Arms

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

Interventions:

• Drug: Daratumumab
• Drug: Pomalidomide
• Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 12, 2020): 21
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2025
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of primary AL amyloidosis of tissue
• Relapsed and/or refractory AL amyloidosis
• 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).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Calculated creatinine clearance ≥ 30 mL/min (see Appendix 11.2).

Exclusion Criteria:

• Non-AL amyloidosis
• Clinically overt myeloma
• Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies or pomalidomide.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kathleen P Research Nurse Coordinator, RN; 646-962-6500; kap9111@med.cornell.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04270175
• Other Study ID Numbers: 19-12021159
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Weill Medical College of Cornell University
• Original Responsible Party: Same as current
• Current Study Sponsor: Weill Medical College of Cornell University
• Original Study Sponsor: Same as current
• Collaborators: Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Cara Rosenbaum, MD; Weill Medical College of Cornell University

• PRS Account: Weill Medical College of Cornell University
• Verification Date: June 2022