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Monoclonal Antibodies

Chemotherapy + Stem Cell Transplant for Amyloidosis

Phase 3

Recruiting

Led By Patrick A Hagen

Research Sponsored by SWOG Cancer Research Network

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

STEP 1: Participants must have systemic AL amyloidosis which is biopsy proven and includes histologically-confirmed by positive Congo red stain with green birefringence on polarized light microscopy, OR characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence). If there is question regarding diagnosis, consult study chairs prior to registration

Monoclonal plasma cells in bone marrow In addition, participants must also have a difference between the involved and uninvolved free light chain (dFLC) >= 2 mg/dL

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of initial registration (step 1) and date of randomization (step 2 registration) to date of first documentation of hematologic pr, vgpr, or cr, assessed up to 4 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares whether adding a stem cell transplant with melphalan after chemotherapy with daratumumab, cyclophosphamide, bortezomib, and dexamethasone (

Who is the study for?

This trial is for adults with newly diagnosed AL amyloidosis, confirmed by specific tests like urine and serum immunofixation electrophoresis, bone marrow analysis, and biopsy. Participants must have a certain level of light chain difference in their blood and can have had up to one cycle of prior therapy. They should be able to perform daily activities on their own or with some effort (ECOG score 0-2) but may be less mobile due to neuropathy.

What is being tested?

The study compares adding stem cell transplant after Dara-VCD chemotherapy (daratumumab, cyclophosphamide, bortezomib, dexamethasone) versus just the chemotherapy for treating AL amyloidosis. The goal is to see if the transplant helps kill more cancer cells when combined with melphalan chemo.

What are the potential side effects?

Potential side effects include reactions from monoclonal antibodies like daratumumab (infusion reactions), effects from steroids such as dexamethasone (immune system suppression), and general chemo side effects like nausea, fatigue, hair loss. Stem cell transplant risks involve infection risk due to immune suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diagnosis of AL amyloidosis is confirmed by biopsy and specific tests.

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My bone marrow has cancerous cells and my blood test shows a specific protein imbalance.

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I am willing to undergo high dose chemotherapy and stem cell transplant if required.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of initial registration (step 1) and date of randomization (step 2 registration) to date of first documentation of hematologic pr, vgpr, or cr, assessed up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of initial registration (step 1) and date of randomization (step 2 registration) to date of first documentation of hematologic pr, vgpr, or cr, assessed up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of initial registration (step 1) and date of randomization (step 2 registration) to date of first documentation of hematologic pr, vgpr, or cr, assessed up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Major organ deterioration progression-free survival (PFS)

Secondary study objectives

Best overall hematologic response

Cardiac and renal organ response rates

Change in patient reported health quality of life (QOL)

+8 more

Other study objectives

Bone marrow Next Generation Flow based MRD negativity rates

Change in PROMIS-29 fatigue domain score

Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 physical function domain

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Maintenance (daratumumab and hyaluronidase-fihj)Experimental Treatment6 Interventions

Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.

Group II: Induction (Chemotherapy)Experimental Treatment13 Interventions

Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI or PET-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.

Group III: Consolidation Arm II (Chemotherapy, ASCT)Experimental Treatment8 Interventions

Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.

Group IV: Consolidation Arm I (Chemotherapy)Active Control9 Interventions

Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dexamethasone

2007

Completed Phase 4

~2650

Bone Marrow Aspiration

2011

Completed Phase 2

~1740