Darzalex Faspro for Blood Cancers

Overseen By Amanda Stevens, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Anti-CD38 therapies

Disqualifiers: COPD, Asthma, HIV, Hepatitis, 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: 4

Duration: 4 weeks

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Darzalex Faspro, a medication targeting specific immune system cells, can lower certain antibodies in people with blood cancers. The aim is to facilitate stem cell transplants from donors for those with high antibody levels, which complicate donor stem cell acceptance. Individuals informed of high donor-specific antibodies preventing transplant may find this trial suitable. As an Early Phase 1 trial, the research seeks to understand the treatment's effects in people, offering participants a chance to contribute to groundbreaking medical advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that Darzalex Faspro, a treatment for certain blood cancers, is generally well-tolerated. A safety review of 898 patients who used Darzalex Faspro identified common side effects such as tiredness, nausea, and fever. These side effects are usually mild and manageable.

Darzalex Faspro has already received approval for other conditions, like multiple myeloma, suggesting its safety for patients. However, each new use of a treatment can produce different effects, making ongoing research important.

Participants should know that while the treatment has been studied, this trial remains in the early stages for this specific use. This means not all possible side effects may be known yet. Those considering joining the trial should consult a healthcare provider to understand the benefits and risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Darzalex Faspro is unique because it combines daratumumab with hyaluronidase-fihj and is administered subcutaneously, meaning it's injected under the skin. This method is more convenient and can be quicker than traditional intravenous (IV) infusions, which are common in current blood cancer treatments. Researchers are excited about its potential to simplify the treatment process while maintaining or even enhancing effectiveness against blood cancers. This approach could offer patients a more comfortable and efficient treatment option compared to standard therapies like IV-administered monoclonal antibodies.

What evidence suggests that Darzalex Faspro might be an effective treatment for blood cancers?

Research shows that Darzalex Faspro targets certain cells in the body that produce antibodies. This trial will administer Darzalex Faspro subcutaneously to participants, followed by a standard desensitization regimen and allogeneic stem cell transplant. In other studies, more than half of the patients treated with Darzalex Faspro for different conditions remained disease-free for a long time. This finding is encouraging for its use in reducing specific antibodies, as it demonstrates the drug's potential in managing antibody-related issues. By neutralizing the problematic cells, Darzalex Faspro could help patients become eligible for transplants by reducing the risk of rejection. ^{4 6 7 8 9}

Who Is on the Research Team?

Christian Gocke

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults with certain blood cancers or conditions like leukemia, lymphoma, and myelodysplastic syndrome who are at high risk of stem cell transplant rejection due to high donor specific antibodies. They must be over 18, willing to participate in a clinical trial, have adequate organ function for the transplant and no other suitable donors.

Inclusion Criteria

All potential Participants must be pre-approved by BMT faculty consensus.

Subjects are eligible if there are high levels of Donor Specific Antibody levels based on protocol specific scoring system regardless of prior attempts at standard desensitization.

Participants must have adequate willingness to participate in a clinical trial.

Exclusion Criteria

Known hypersensitivity or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients.

My lung function is less than half of what is expected for someone my age and size.

I have been treated with Daratumumab or another anti-CD38 therapy before.

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 Darzalex Faspro followed by standard desensitization regimen and allogeneic stem cell transplant

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of DSA levels and recovery metrics

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Darzalex Faspro

Trial Overview The study tests Darzalex Faspro's ability to lower donor specific antibody levels enough for patients to undergo an allogeneic peripheral blood stem cell transplant safely. It aims to see if this treatment can prevent the rejection of transplanted cells in those at high risk.

How Is the Trial Designed?

Group I: Daratumumab-SC followed by standard of care DSA desensitization and alloBMT Experimental Treatment 2 Interventions

Darzalex Faspro (Daratumumab and hyaluronidase-fihj) will be administered subcutaneously (SC) weekly (every 7 day +/- 1 day) for a total of four doses followed by standard desensitization regimen and allogeneic stem cell transplant.

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

Approved in United States as Darzalex Faspro for:

• Newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone
• Relapsed or refractory multiple myeloma in combination with pomalidomide and dexamethasone
• Relapsed or refractory multiple myeloma in combination with carfilzomib and dexamethasone
• Monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent

Approved in European Union as Darzalex for:

• Multiple myeloma in combination with lenalidomide and dexamethasone
• Multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone
• Relapsed or refractory multiple myeloma in combination with pomalidomide and dexamethasone
• Monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

In a study of 40 men with hormone refractory prostate cancer, the combination of docetaxel, vinorelbine, and zoledronic acid showed promising results, with 18% achieving complete PSA responses and 32% showing major PSA responses after treatment.

The treatment was well tolerated, with manageable side effects; the median overall survival was 17 months, and nearly half of the patients experienced a reduction in pain intensity and analgesic use after two cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, vinorelbine, and zoledronic acid as first-line treatment in patients with hormone refractory prostate cancer: a phase II study. Di Lorenzo, G., Autorino, R., Perdonà, S., et al.[2018]

The study found that dendritic cell (DC)-tumor fusion vaccines are more effective than traditional DC vaccines sensitized with tumor lysates in treating hormone-refractory prostate cancer (HRPC), as indicated by higher levels of IL-12 and interferon-gamma production.

In functional assays, T cells activated by the DC-tumor fusion vaccine demonstrated significantly greater tumor-killing activity compared to those activated by DCs pulsed with tumor lysates, suggesting enhanced efficacy of the fusion vaccine approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The establishment of dendritic cell-tumor fusion vaccines for hormone refractory prostate cancer cell. Kim, TB., Park, HK., Chang, JH., et al.[2021]

Denosumab is a new bone-protective agent that has been shown to be more effective than the previously standard treatment, zoledronic acid, in managing skeletal-related events in patients with castration-resistant prostate cancer (CRPC).

The review also evaluates the cost-effectiveness of denosumab, highlighting its similar rate of adverse effects compared to zoledronic acid, making it a favorable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of denosumab as a bone protective agent for patients with castration resistant prostate cancer. Dellis, A., Papatsoris, A.[2018]

The combination of daratumumab, bortezomib, and dexamethasone (Dvd) significantly enhances the effectiveness of expanded natural killer (NK) cells in targeting multiple myeloma, as shown in a mouse model.

Dvd treatment not only increased the cytotoxicity of NK cells but also improved their persistence and ability to home to tumor sites, leading to reduced tumor burden and prolonged survival in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model. Thangaraj, JL., Ahn, SY., Jung, SH., et al.[2023]

FcRL5 is highly expressed on plasma cells in multiple myeloma, making it a promising target for antibody-drug conjugates (ADCs) that can selectively deliver cytotoxic drugs to cancer cells while minimizing effects on normal tissues.

Two specific ADCs targeting FcRL5 demonstrated significant efficacy in both laboratory and animal models, especially when used in combination with existing myeloma treatments like bortezomib or lenalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. Elkins, K., Zheng, B., Go, M., et al.[2020]

Daratumumab (DARA), a therapeutic antibody targeting CD38, can induce programmed cell death in multiple myeloma cells when cross-linked by secondary antibodies or Fcγ receptors, highlighting its potential effectiveness in treating this cancer.

In both in vitro and in vivo studies, the activation of both inhibitory and activating Fcγ receptors was shown to facilitate this cell death, suggesting that FcγR-mediated cross-linking is a key mechanism contributing to the therapeutic activity of DARA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic CD38 Monoclonal Antibody Daratumumab Induces Programmed Cell Death via Fcγ Receptor-Mediated Cross-Linking. Overdijk, MB., Jansen, JH., Nederend, M., et al.[2022]

Daratumumab, an anti-CD38 antibody, shows strong anti-tumor activity in various types of non-Hodgkin lymphoma (NHL), including mantle cell lymphoma (MCL) and follicular lymphoma (FL), both in laboratory models and in vivo, effectively preventing tumor growth and improving overall survival.

The drug enhances the effectiveness of standard chemotherapy regimens (CHOP and R-CHOP) in treating MCL and FL, demonstrating its potential as a valuable addition to existing therapies for these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens. Vidal-Crespo, A., Matas-Céspedes, A., Rodriguez, V., et al.[2022]

In a phase III trial involving 462 patients with metastatic renal cell carcinoma, Rocapuldencel-T combined with standard treatment did not significantly improve overall survival compared to standard treatment alone, with median overall survival of 27.7 months for the combination group versus 32.4 months for the standard treatment group.

Despite the lack of overall survival benefit, 70% of patients receiving Rocapuldencel-T showed immune responses, which correlated positively with overall survival, suggesting that while the therapy may not extend life, it can stimulate the immune system in a meaningful way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma. Figlin, RA., Tannir, NM., Uzzo, RG., et al.[2021]

The treatment landscape for castration-resistant prostate cancer (CRPC) has expanded significantly in the last two years, with four new approved drugs and an upcoming immunotherapy option, sipuleucel-T, enhancing treatment options beyond traditional chemotherapy with docetaxel.

For asymptomatic or minimally symptomatic CRPC patients who have not undergone chemotherapy, the androgen biosynthesis inhibitor abiraterone has demonstrated a significant survival benefit, while other treatments like enzalutamide and cabazitaxel have shown effectiveness for patients whose disease has progressed after docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapy concepts for castration-resistant prostate cancer: between hormone manipulation, targeted therapy and chemotherapy]. Kübler, H., Miller, K.[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]

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 ... More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06398457

Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) ... The primary endpoint will be based on safety of Darzalex Faspro and the number of patients who have DSA levels lowered enough to proceed to conditioning based ...

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-faspro-daratumumab-and-hyaluronidase

DARZALEX FASPRO® (daratumumab and hyaluronidase) The most common (≥20%) grade 3/4 TEAEs with D-Rd vs Rd were neutropenia (54.1% vs 37.0%, respectively) and anemia (17.0% vs 21.6%, respectively) ...

4. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... Targeting plasma cells with daratumumab aids in the treatment of post-transplant autoimmune-like hepatitis. Pediatr Blood Cancer. 2021;68(11):e29290 ...

5. cancerletter.com cancerletter.com/clinical-roundup/20241213_9i/

Darzalex Faspro-based regimens demonstrate improved ... Johnson & Johnson announced data highlighting that Darzalex Faspro (daratumumab and hyaluronidase-fihj)-based regimens improve overall and ...

6. 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® A summary of safety data regarding the occurrence of hematologic events in patients receiving DARZALEX® (daratumumab) and DARZALEX FASPRO® ...

7. darzalex.com darzalex.com/isi/

Important Safety Information for DARZALEX® FASPRO Find important safety information for DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). See Full Prescribing and Safety Information.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.gov In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy ...

9. darzalexhcp.com darzalexhcp.com/

DARZALEX® (daratumumab) & DARZALEX FASPRO ... In addition to the safety data presented in the study, here is some other safety information to consider in older patients across the DARZALEX® clinical trials.