Clinical trial NCT04270175: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Amyloid
AL Amyloidosis
Refractory AL Amyloidosis
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2020-02-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Overall Complete Hematologic Response
timeFrame: Follow-up for up to 1 year
Secondary outcomes:
measure: Duration of Very Good Partial Response (VGPR) or better hematologic response rates
timeFrame: Follow-up for up to 5 years
measure: Low-dFLC Partial Response Rate (applicable to low-dFLC pt group)
timeFrame: Follow-up for up to 1 year
measure: Percentage of participants with an Organ Response
timeFrame: Follow-up for up to 3 years
measure: Median estimate of months that participants have Progression Free Survival
timeFrame: Follow-up for up to 5 years
measure: Median number of months of participant's Overall Survival
timeFrame: Follow-up for up to 5 years
measure: Time to Complete Hematologic Response
timeFrame: Follow-up for up to 1 year
measure: Time to Hematologic Progression
timeFrame: Follow-up for up to 5 years
measure: Time until Next Treatment Therapy
timeFrame: Follow-up for up to 5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medicine - Multiple Myeloma Center
state: New York
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Weill Medical College of Cornell University
name: Cara Rosenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: