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

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.

Study Overview

• Status: Recruiting
• Conditions: AL Amyloidosis; Amyloid; Refractory AL Amyloidosis
• Intervention / Treatment: Drug: Pomalidomide; Drug: Daratumumab SC; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kathleen P Research Nurse Coordinator, RN; Phone Number: 646-962-6500; Email: kap9111@med.cornell.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Michaela Liedtke, MD; Email: Mliedtke@Stanford.edu
      • Principal Investigator: Michaela Liedtke, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University Medical Center
      • Principal Investigator: Vaishali Sanchorawala, MD
      • Contact: Vaishali Sanchorawala, MD; Email: Vaishali.Sanchorawala@bmc.org
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine - Multiple Myeloma Center
      • Principal Investigator: Cara Rosenbaum, MD
      • Contact: Research Nurse Coordinator; Phone Number: 646-962-6500; Email: kap9111@med.cornell.edu
      • Contact: Research Nurse Coordinator; Phone Number: (646) 962-6500; Email: naa9101@med.cornell.edu
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Principal Investigator: Anita D'Souza, MD
      • Contact: Anita D'Souza, MD; Email: anitadsouza@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Pomalidomide; Given as 4mg oral capsule; Drug: Daratumumab SC; Given as 1800mg via injection; Other Names: Faspro; Drug: Dexamethasone; Given as 20mg or 40 mg IV and 20mg or 40mg oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Cara Rosenbaum, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 2, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Paraproteinemias; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Daratumumab
• Other Study ID Numbers: 19-12021159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No