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

Plain English Summary

Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab is a Phase 2 clinical trial sponsored by Weill Medical College of Cornell University studying Amyloid, AL Amyloidosis, Refractory AL Amyloidosis. This trial tests a combination of three drugs: daratumumab, pomalidomide, and dexamethasone (DPd). It is for adults with AL amyloidosis that has returned or not responded to previous treatment, and who have previously received daratumumab. Participation involves receiving the study drugs and regular medical check-ups. Alternative treatments may include other chemotherapy regimens or supportive care. The trial aims to enroll 15 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with AL amyloidosis that has relapsed or is refractory (not responding to treatment). Patients must have previously received daratumumab. Patients must have measurable disease and be able to provide consent. Exclusion criteria include other types of amyloidosis, active myeloma, or significant heart or lung disease. This trial is studying Amyloid, AL Amyloidosis, Refractory AL Amyloidosis, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the percentage of patients who achieve a complete remission, meaning their disease is undetectable, which is a key goal for long-term control. The specific primary outcome measures are: Percentage of Participants With Overall Complete Hematologic Response (Follow-up for up to 1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical unmet need for patients with relapsed/refractory AL amyloidosis who have progressed after daratumumab, aiming to improve treatment outcomes in this challenging populati Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Amyloid, AL Amyloidosis, Refractory AL Amyloidosis, where improved treatment options are needed.

Investor Insight

This trial targets a rare but serious condition, and success could lead to a new treatment option, potentially impacting a niche but significant market for hematologic malignancies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, considering your specific medical history and previous treatments. Participation involves regular visits for drug administration, blood tests, and monitoring for side effects. You will be closely monitored for your response to treatment and any adverse events. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 15 participants

Interventions

• DRUG: Daratumumab SC — 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 tablet.

Primary Outcomes

• Percentage of Participants With Overall Complete Hematologic Response (Follow-up for up to 1 year)

Secondary Outcomes

• Duration of Very Good Partial Response (VGPR) or better hematologic response rates (Follow-up for up to 5 years)
• Low-dFLC Partial Response Rate (applicable to low-dFLC pt group) (Follow-up for up to 1 year)
• Percentage of participants with an Organ Response (Follow-up for up to 3 years)
• Median estimate of months that participants have Progression Free Survival (Follow-up for up to 5 years)
• Median number of months of participant's Overall Survival (Follow-up for up to 5 years)

Full 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.

Trial Locations

• Stanford University, Palo Alto, California, United States
• Boston University Medical Center, Boston, Massachusetts, United States
• Weill Cornell Medicine - Multiple Myeloma Center, New York, New York, United States
• Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Frequently Asked Questions

Related Conditions

• AL Amyloidosis
• Light Chain Amyloidosis
• Relapsed Amyloidosis
• Refractory Amyloidosis
• Multiple Myeloma
• Plasma Cell Disorders
• Hematologic Malignancies
• Monoclonal Gammopathy
• Amyloidosis
• Waldenstrom Macroglobulinemia

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