Daratumumab Combination for Multiple Myeloma

Overseen By Muzaffar Qazilbash

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: Unknown

Duration: 3 years

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies whether daratumumab and hyaluronidase-fihj and pomalidomide work in treating patients with multiple myeloma that has come back (relapsed) after stem cell transplant. Daratumumab and hyaluronidase-fihj is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab and hyaluronidase-fihj with pomalidomide may help control the disease in patients with relapsed multiple myeloma.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Daratumumab for treating multiple myeloma?

Research shows that Daratumumab, when combined with other drugs like lenalidomide and dexamethasone, significantly improves the time patients live without their disease getting worse and increases the number of patients who respond well to treatment. It has been effective in both newly diagnosed and relapsed multiple myeloma cases, with manageable side effects. ^{1 2 3 4 5}

Is daratumumab safe for humans?

Daratumumab, used for treating multiple myeloma, has shown a generally acceptable safety profile in clinical trials, with common side effects including blood-related issues like neutropenia (low white blood cell count) and lymphopenia (low lymphocyte count). It has been tested both as a single treatment and in combination with other drugs, and while it has some side effects, it is considered safe enough for use in humans. ^{1 3 5 6 7}

How is the drug Daratumumab unique for treating multiple myeloma?

Daratumumab is unique because it is a first-in-class monoclonal antibody that targets the CD38 protein on multiple myeloma cells, leading to their destruction through several mechanisms. It can be administered intravenously or subcutaneously, and when combined with other drugs, it has shown to significantly prolong progression-free survival in patients, offering a novel option for those who have relapsed or are newly diagnosed. ^{1 2 3 5 8}

Research Team

Muzaffar Qazilbash, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with relapsed multiple myeloma post-stem cell transplant. They must have had a partial response to salvage therapy, be within 60-180 days post-transplant, and have an ECOG status of 0-2. Key eligibility includes adequate kidney function (creatinine <= 2.5 mg/dL), platelet count >= 50,000/mm^3, neutrophil count >= 1000/mm^3, liver enzymes up to three times the normal limit, and no uncontrolled heart arrhythmias.

Inclusion Criteria

Your liver enzyme levels are not more than three times the normal limit.

My condition worsened after initial treatment but improved with further therapy.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have not had radiotherapy in the last 14 days.

I am currently pregnant or breastfeeding.

I have tested positive for hepatitis B surface antigen or have resolved hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and hyaluronidase-fihj subcutaneously and pomalidomide orally in cycles every 28 days for up to 3 years

3 years

Frequent visits during initial cycles, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks after initial follow-up at 30 and 90 days

Treatment Details

Interventions

• Daratumumab

Trial Overview The study tests daratumumab with hyaluronidase-fihj and pomalidomide in treating relapsed multiple myeloma after stem cell transplant. Daratumumab is designed to stop cancer cells from growing by targeting specific proteins on their surface while pomalidomide aims to kill or halt the division of cancer cells.

Participant Groups

Group I: Treatment (daratumumab) Experimental Treatment 1 Intervention

Beginning 60-120 days after transplant, participants receive daratumumab IV over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6, then on day 1 of subsequent courses. Courses repeat every 28 days for 3 years in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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 the POLLUX study, after 25.4 months of follow-up, the combination of daratumumab with lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma, with a hazard ratio of 0.41 compared to lenalidomide/dexamethasone alone.

The overall response rate was notably higher with the daratumumab combination (92.9%) compared to the control (76.4%), and a significant proportion of patients achieved minimal residual disease negativity (26.2% vs 6.4%), indicating a deeper response without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Dimopoulos, MA., San-Miguel, J., Belch, A., et al.[2019]

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]

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.

Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. [2018]

4. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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