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

Weill Cornell Medicine (WCM)

Status and phase: Active, not recruiting; Phase 2

Conditions: Refractory AL Amyloidosis; AL Amyloidosis; Amyloid

Treatments: Drug: Daratumumab SC; Drug: Dexamethasone; Drug: Pomalidomide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04270175

19-12021159

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

15 participants in 1 patient group

daratumumab/pomalidomide/dexamethasone

Experimental group

Description:

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

Treatment:

Drug: Pomalidomide

Drug: Dexamethasone

Drug: Daratumumab SC