Daratumumab for Hemolytic Anemia

(DARA-AIHA Trial)

Overseen By Research Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dartmouth-Hitchcock Medical Center

Must be taking: Steroids, Rituximab

Must not be taking: Anti-CD38 therapies

Disqualifiers: HIV, Hepatitis, Lupus, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial tests a medication called daratumumab (also known as Darzalex) to determine its effectiveness for autoimmune hemolytic anemia, a condition where the body destroys its own red blood cells, causing fatigue and shortness of breath. Participants will receive weekly doses to assess symptom reduction. This trial suits individuals who have tried steroids and rituximab without success and still experience symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially beneficial treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does allow patients to continue using steroids as part of their standard care. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that daratumumab, a treatment for multiple myeloma (a type of blood cancer), is generally safe and well-tolerated. Patients often experience mild side effects, such as reactions at the injection site, occurring in about 7% of cases. Most reactions are not serious. However, serious issues have arisen in patients with autoimmune hemolytic anemia (a condition where the immune system attacks red blood cells). Two patients died from severe hemolytic anemia after starting treatment with daratumumab.

While daratumumab appears promising, especially for various conditions, these risks should be considered for those with autoimmune hemolytic anemia. Discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for hemolytic anemia, which often involve steroids or immunosuppressants, daratumumab is an exciting new option because it directly targets CD38, a protein found on the surface of many blood cells. This targeted approach means daratumumab can potentially reduce the destruction of red blood cells more effectively. Additionally, it is administered subcutaneously, which is less invasive compared to intravenous options, making the treatment more convenient for patients. Researchers are particularly optimistic because this method could offer a quicker and more direct way to manage hemolytic anemia.

What evidence suggests that daratumumab might be an effective treatment for hemolytic anemia?

Research has shown that daratumumab effectively treats conditions like multiple myeloma, helping patients live longer without disease progression. In studies, 60% of patients using daratumumab achieved MRD negativity, indicating no detectable signs of the disease and suggesting successful treatment. In this trial, participants will receive six weekly doses of subcutaneous daratumumab to evaluate its potential in treating autoimmune hemolytic anemia (AIHA). Although limited information exists on using daratumumab specifically for AIHA, it is under study because it targets and reduces harmful immune cells. This suggests it might help manage AIHA, although results are still being gathered. ^{1 2 3 4 5}

Who Is on the Research Team?

Matthew Sullivan, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

Adults with confirmed autoimmune hemolytic anemia who have tried steroids and rituximab without success are eligible for this trial. They must not have severe kidney failure, recent heart issues, uncontrolled medical conditions, active infections like HIV or Hepatitis B/C, certain lung diseases, end-stage liver disease, active lupus with systemic involvement, or untreated lymphoid malignancy.

Inclusion Criteria

Patients must give informed consent indicating awareness of the investigational nature of the treatment and study protocols

I am taking steroids as part of my standard treatment.

My blood cells continue to break down despite treatment or while on Prednisone.

Exclusion Criteria

I have active Lupus affecting my organs and need treatment.

I do not have any serious uncontrolled illnesses, infections, or major heart problems.

My liver is in its final stage of disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive six weekly doses of subcutaneous daratumumab 1,800mg and hyaluronidase 30,000U

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measuring daratumumab levels and anti-RBC antibody levels

12 weeks

Visits at 14 and 28 days post-treatment

Long-term follow-up

Participants are monitored for time to next treatment and overall response rate

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The study is testing the safety of Daratumumab/Hyaluronidase injection in patients with refractory Autoimmune Hemolytic Anemia. It's a single-arm trial where all participants receive the same treatment to see how well it works when other treatments haven't helped.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

Six weekly doses of subcutaneous daratumumab 1,800mg and hyaluronidase 30,000U.

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Citations

1. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-and-darzalex-faspro-use-for-the-treatment-of-autoimmune-hemolytic-anemia

Use for the Treatment of Autoimmune Hemolytic Anemia Two patients (1 each with warm AIHA and cold AIHA) died 3 months after the start of DARZALEX due to uncontrolled severe hemolytic anemia.

2. aetna.com aetna.com/cpb/medical/data/900_999/0904.html

Daratumumab (Darzalex) and Daratumumab and ... Efficacy results were based on ORR as determined by the Independent Review Committee assessment using the International Myeloma Working Group (IMWG) criteria.

3. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... Data from Phase 3 CEPHEUS study show 60 percent overall MRD negativity (10−5) and improved PFS with DARZALEX FASPRO® in transplant-ineligible ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05004259

The Safety of Repurposing Daratumumab for Relapsed or ... A single-arm study utilizing a 6 x 4 expansion design using daratumumab SC treatment for patients with refractory Autoimmune Hemolytic Anemia. Detailed ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/761145Orig1s000MultidisciplineR.pdf

761145Orig1s000 - accessdata.fda.gov Daratumumab SC as Monotherapy. Integrated efficacy data were presented from 553 subjects assigned to receive daratumumab SC or IV monotherapy ...