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Trial record 1 of 1 for:    NCT04270175
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Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab

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ClinicalTrials.gov Identifier: NCT04270175
Recruitment Status : Not yet recruiting
First Posted : February 17, 2020
Last Update Posted : January 26, 2021
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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
Amyloid AL Amyloidosis Refractory AL Amyloidosis Drug: Daratumumab Drug: Pomalidomide Drug: Dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2025


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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Median estimate of months that participants have progression free survival [ Time Frame: Approximately 5 years ]
    Median estimate calculated using the Kaplan-Meier methodology

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04270175


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

Locations
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United States, California
Stanford University
Palo Alto, California, United States, 94304
Contact: Michaela Liedtke, MD       mliedtke@stanford.edu   
Principal Investigator: Michaela Liedtke, MD         
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Contact: Vaishali Sanchorawala, MD       Vaishali.Sanchorawala@bmc.org   
Principal Investigator: Vaishali Sanchorawala, MD         
United States, New York
Weill Cornell Medicine - Multiple Myeloma Center
New York, New York, United States, 10065
Contact: Research Nurse Coordinator    646-962-6500    kap9111@med.cornell.edu   
Contact: Research Nurse Coordinator    (646) 962-6500    naa9101@med.cornell.edu   
Principal Investigator: Cara Rosenbaum, MD         
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Contact: Anita D'Souza, MD       anitadsouza@mcw.edu   
Principal Investigator: Anita D'Souza, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Cara Rosenbaum, MD Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT04270175    
Other Study ID Numbers: 19-12021159
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: January 26, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias
Dexamethasone
Pomalidomide
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors