Monoclonal Antibody + Chemotherapy + Radiation for Stem Cell Transplant in Multiple Myeloma

Overseen By Phuong Vo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Anti-CD38 antibodies, Checkpoint inhibitors

Disqualifiers: CNS involvement, Coronary artery disease, Asthma, HIV, others

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

Compensation: Varies

Number of Visits: 9

Duration: Approximately 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for patients with high-risk multiple myeloma that is newly diagnosed, recurrent, or unresponsive to treatment. It combines a monoclonal antibody linked to a radioactive agent with chemotherapy and low-dose radiation before a stem cell transplant to determine if this approach effectively kills cancer cells and prepares the bone marrow for new healthy cells. The trial includes two groups, each receiving a slightly different combination of these treatments. People with multiple myeloma, especially those with specific genetic features or a history of certain conditions, might be suitable candidates for this trial. 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 innovative approach.

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 anti-CD38 monoclonal antibody therapy, you must stop it at least 3 months before the infusion of ²¹¹At-OKT10-B10.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like ²¹¹At-OKT10-B10, fludarabine, cyclophosphamide, and total-body irradiation (TBI) are under study for safety in treating multiple myeloma, a type of cancer. Early results suggest that ²¹¹At-OKT10-B10 can effectively target and kill cancer cells. This treatment has shown promise in extending life in animal studies, though research in humans continues.

Cyclophosphamide, a chemotherapy drug, is generally well-tolerated but can cause low blood cell counts, a common issue in cancer treatments. Most patients do not experience severe side effects.

Fludarabine, another chemotherapy drug in this trial, has caused some blood-related side effects like low white blood cell counts in past studies, but these can be managed with proper medical care.

TBI uses radiation to kill cancer cells. Some studies report it can lead to remission, a period without symptoms, in some patients. However, like other radiation treatments, it can have side effects, including fatigue and low blood counts.

This trial is in an early phase, focusing on finding the safest dose. Early trials often prioritize examining side effects over effectiveness. ²¹¹At-OKT10-B10 and the other treatments are being carefully tested to ensure safety before wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple myeloma, which typically involve chemotherapy and autologous stem cell transplants, these investigational treatments introduce a novel approach using the Astatine At 211 Anti-CD38 Monoclonal Antibody, OKT10-B10. This antibody specifically targets CD38, a protein found on the surface of multiple myeloma cells, potentially enhancing the effectiveness of the treatment by directly attacking the cancer cells. Additionally, the combination of this targeted approach with traditional chemotherapy, like fludarabine and cyclophosphamide, and total-body irradiation (TBI) might improve outcomes by maximizing the destruction of malignant cells while preparing the body for a stem cell transplant. Researchers are excited about this trial because it could offer a more targeted and potentially more effective treatment option for patients with multiple myeloma.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research shows that the monoclonal antibody ²¹¹At-OKT10-B10 targets cancer cells in multiple myeloma by attaching to a protein called CD38, delivering radiation directly to the cancer cells to potentially destroy them. In earlier studies with mice, this treatment more than doubled survival time compared to those not treated. In this trial, participants in Arm A will receive ²¹¹At-OKT10-B10, fludarabine, total-body irradiation (TBI), and allogeneic hematopoietic stem cell transplantation (HCT). Participants in Arm B will receive ²¹¹At-OKT10-B10, fludarabine, cyclophosphamide, TBI, and HCT. Fludarabine and cyclophosphamide are chemotherapy drugs that stop cancer cells from growing and dividing. Radiation therapy also helps kill cancer cells and shrink tumors. Combining these treatments before a stem cell transplant aims to eliminate cancer cells and prepare the body for new, healthy cells. ^{1 2 3 4 6}

Who Is on the Research Team?

Phuong Vo

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with high-risk multiple myeloma, either newly diagnosed or not responding to treatment. Participants must have specific genetic features of the cancer, good organ function, and a matched stem cell donor available. Pregnant women, those unable to consent, and individuals with certain medical conditions or treatments are excluded.

Inclusion Criteria

My cancer cells are plasmablastic in nature.

I have had plasma cell leukemia before.

I have been diagnosed with multiple myeloma for the first time or it has returned.

Exclusion Criteria

You may not be able to handle medical tests or treatments.

I cannot receive radiotherapy due to health reasons.

I have received high-dose radiation to my pelvis or a critical organ.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ²¹¹At-OKT10-B10, fludarabine, and possibly cyclophosphamide, followed by TBI and allogeneic HCT

Approximately 2 weeks

Daily visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 9, 12, 18, and 24 months

24 months

Periodic visits at 9, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
• Cyclophosphamide
• Fludarabine Phosphate
• Total-Body Irradiation

Trial Overview The trial tests a radioactive antibody (²¹¹At-OKT10-B10) combined with chemotherapy (fludarabine alone or with cyclophosphamide) and low-dose total-body irradiation before a stem cell transplant. The goal is to see how well this regimen kills cancer cells and prepares the body for new healthy blood-forming cells.

How Is the Trial Designed?

Group I: Arm B (²¹¹At-OKT10-B10, chemotherapy, TBI, HCT) Experimental Treatment 9 Interventions

Patients with HLA-matched haploidentical donors receive ²¹¹At-OKT10-B10 IV on day -8 (day -14 to -7), fludarabine IV over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on day -6 and -5. Patients then undergo TBI on day -1 and allogeneic HCT on day 0. Additionally, patients undergo x-rays on study, and blood sample collection, bone marrow biopsy, and bone marrow aspiration throughout the study.

Group II: Arm A (²¹¹At-OKT10-B10, fludarabine, TBI, HCT) Experimental Treatment 8 Interventions

Patients with HLA-matched related or unrelated donors receive ²¹¹At-OKT10-B10 IV on day -7 (day -10 to -5) and fludarabine IV over 30 minutes on days -4 to -2. Patients then undergo TBI and allogeneic HCT on day 0. Additionally, patients undergo x-rays on study, and blood sample collection, bone marrow biopsy, and bone marrow aspiration throughout the study.

Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6788008/

The α-emitter astatine-211 targeted to CD38 can eradicate ... These data suggest that 211At-CD38 offers the potential to eliminate residual MM cell clones in low-disease-burden settings, including MRD. We are optimistic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649711937990X

The Alpha Emitter Astatine-211 Targeted to CD38 Can ... In murine therapy studies, 211At-CD38 RIT at 15 - 45 µCi at least doubled median survival relative to untreated controls in each of two MM SQ ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04579523

NCT04579523 | ²¹¹At-OKT10-B10 and Fludarabine Alone ... OKT10-B10 attaches to CD38 positive cancer cells in a targeted way and delivers ²¹¹At to kill them.

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/astatine-at-211-anti-cd38-monoclonal-antibody-okt10-b10?pn=1

Clinical Trials Using Astatine At 211 Anti-CD38 Monoclonal ... Review the clinical trials studying astatine at 211 anti-cd38 monoclonal antibody okt10-b10 on this list and use the filters to refine the results by age ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04466475

NCT04466475 | Radioimmunotherapy (211At-OKT10-B10 ... This phase I trial studies the side effects and best dose of 211At-OKT10-B10 when given together with melphalan before a stem cell transplantation in ...

6. withpower.com withpower.com/trial/phase-1-neoplasms-plasma-cell-1-2022-828a5

Monoclonal Antibody + Chemotherapy + Radiation for Stem Cell ... Research shows that the α-emitter astatine-211, when targeted to CD38, can significantly extend survival in a mouse model of multiple myeloma by effectively ...