Daratumumab for Leukemia

Overseen By Shira Dinner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eastern Cooperative Oncology Group

Disqualifiers: Pregnancy, Breastfeeding, GVHD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 4

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of daratumumab-hyaluronidase in treating T-cell acute lymphoblastic leukemia (T-ALL) in individuals whose minimal residual disease (MRD) persists or returns after chemotherapy. The goal is to determine if this treatment can effectively target and eliminate leukemia cells remaining after standard treatment. Participants must have T-ALL, be in remission following chemotherapy, and still show signs of MRD, indicating detectable leukemia cells. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant advancements in leukemia treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy for Grafts Versus Host Disease (GVHD), you may not be eligible, except for prednisone at a dose of 10 mg or less per day.

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

Previous studies have generally shown that patients tolerate daratumumab well. The most common side effect, an upper respiratory tract infection, occurred in 20% or more of patients, potentially making colds more likely. Injection site reactions, such as redness or swelling, occurred in about 7% of patients. More serious side effects include changes in blood cell counts, such as low white blood cells (neutropenia), affecting about 44% of patients, which can hinder the body's ability to fight infections. Overall, daratumumab has been used safely in other conditions, offering some confidence in its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Unlike standard chemotherapy options for leukemia, Daratumumab is unique because it specifically targets and binds to the CD38 protein on cancer cells, helping the immune system destroy them. This targeted approach can potentially lead to fewer side effects compared to traditional treatments. Additionally, Daratumumab is combined with hyaluronidase, which allows for a faster and more comfortable subcutaneous administration, making the treatment process less burdensome for patients. Researchers are excited about Daratumumab because it offers a more precise and possibly gentler alternative to current leukemia treatments.

What evidence suggests that daratumumab might be an effective treatment for T-ALL?

Research has shown that daratumumab-hyaluronidase, the treatment under study in this trial, holds promise for treating blood cancers. This treatment effectively reduces cancer cells, achieving minimal residual disease (MRD) negativity. Studies have found that about 91% of patients responded well when daratumumab was combined with other drugs for similar blood conditions. Although specific information on T-cell acute lymphoblastic leukemia (T-ALL) is limited, the drug's success in related conditions suggests potential effectiveness. This indicates that daratumumab-hyaluronidase might help treat T-ALL, particularly in patients with ongoing or returning MRD. ^{2 4 5 6 7}

Who Is on the Research Team?

Shira Dinner, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for people with T-cell ALL who still have cancer cells after chemotherapy (MRD ≥ 10-4). They can't be pregnant or breastfeeding, must not have severe heart disease, active brain cancer involvement, uncontrolled HIV/HBV/HCV infections, or need strong drugs for GVHD. Good organ function and a performance status of 0-2 are required.

Inclusion Criteria

I have another cancer type, but it won't affect this trial's treatment.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I have T cell ALL and am in remission after intensive chemotherapy.

Exclusion Criteria

Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weekly doses of daratumumab-hyaluronidase

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of MRD status on Day 64

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The study tests daratumumab-hyaluronidase injection in patients with T-cell ALL who haven't responded well to chemotherapy. It aims to see if this treatment can eliminate the remaining cancer cells that standard therapy didn't get rid of.

How Is the Trial Designed?

Group I: Course 1 Experimental Treatment 1 Intervention

Daratumumab-hyaluronidase

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?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

In a phase 1/2 study involving 31 patients with relapsed chronic lymphocytic leukemia (CLL), the addition of lumiliximab to the standard FCR treatment resulted in a high overall response rate of 65%, with 52% achieving a complete response, indicating enhanced efficacy compared to FCR alone.

The combination therapy maintained a similar toxicity profile to FCR alone, suggesting that lumiliximab can be safely added to the treatment regimen without increasing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Byrd, JC., Kipps, TJ., Flinn, IW., et al.[2021]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

About 30% of the 1012 patients studied received rituximab off-label for conditions like rheumatoid arthritis, indicating its widespread use beyond approved indications.

Most patients were unaware of the risk of progressive multifocal leukoencephalopathy (PML) associated with rituximab, with only 32.8% receiving the Patient Alert Card (PAC) designed to inform them about this risk, although those who did receive the PAC had better awareness of PML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card. Sarsour, K., Beckley-Kartey, S., Melega, S., et al.[2020]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.3% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma during the phase II LOTIS-2 trial, indicating its efficacy as a treatment option.

The drug demonstrated a tolerable safety profile with common side effects including neutropenia and thrombocytopenia, and no new safety concerns were identified in the phase II trial, suggesting it is safe for further testing in various non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. Zurko, J., Hamadani, M.[2021]

Monoclonal antibody therapies for advanced primary cutaneous lymphomas show promising efficacy and a more manageable safety profile compared to traditional polychemotherapy, which often has severe side effects.

Despite their advantages, the safety of these monoclonal antibodies must be carefully evaluated, as adverse effects can arise from targeting not only tumor cells but also benign T and B cells, and many patients have undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Reactions of Antibody-Therapy for Primary Cutaneous Lymphomas: Rituximab, Brentuximab Vedotin, Alemtuzumab, and Mogamulizumab. Saulite, I., Guenova, E., Hoetzenecker, W.[2019]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

In a phase 3 trial with 569 patients, the addition of daratumumab to lenalidomide and dexamethasone significantly improved progression-free survival, with only 18.5% of patients experiencing disease progression compared to 41.0% in the control group.

Daratumumab also resulted in a higher overall response rate (92.9% vs. 76.4%) and a greater percentage of patients achieving minimal residual disease status (22.4% vs. 4.6%), although it was associated with a higher incidence of neutropenia and infusion-related reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Oriol, A., Nahi, H., et al.[2022]

The FDA has issued a warning about an increased risk of death associated with duvelisib (Copiktra) compared to the monoclonal antibody ofatumumab in treating chronic lymphocytic leukemia.

Patients using duvelisib are also at a higher risk for serious adverse effects, necessitating close monitoring by healthcare providers and reporting of any adverse events to the FDA's MedWatch program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible Increased Risk of Death from Blood Cancer Drug. Aschenbrenner, DS.[2023]

Citations

1. 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 ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

2. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/use-of-darzalex-darzalex-faspro-in-acute-lymphoblastic-leukemia-or-acute-lymphoblastic-lymphoma

DARZALEX® (daratumumab) No patients achieved CR within 2 treatment cycles. · One patient achieved CRi, 3 patients had refractory acute lymphoblastic leukemia, and 3 ...

3. darzalex.com darzalex.com/clinical-results/

Clinical Results 91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141371/

Real-world data on the use of subcutaneous daratumumab ... As of the data cutoff (August 8, 2023), 49 patients were included. By the end of consolidation, 91.7% of patients achieved an overall response ( ...

5. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/fda-approval-new-treatment-indication-multiple-myeloma-drug

New Treatment Indication for Multiple Myeloma Drug Participants who received daratumumab plus hyaluronidase with Pd had significantly reduced risk of disease progression or death by 37% compared to participants ...

6. darzalexhcp.com darzalexhcp.com/

HCP Website | DARZALEX® (daratumumab) & ... In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse ...

7. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/darzalex-darzalex-faspro-adverse-event-hematologic-events-in-patients-with-newly-diagnosed-multip

Adverse Event - DARZALEX FASPRO® The most common grade 3/4 hematologic treatment-emergent adverse events (TEAEs) were neutropenia (43.8%), lymphopenia (31.3%), and thrombocytopenia (25.0%).