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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial investigates the side effects and best dose of ²¹¹At-OKT10-B10 when given together with fludarabine, alone or in combination with cyclophosphamide and low-dose total-body irradiation (TBI) before donor stem cell transplant in treating patients with high-risk multiple myeloma that is newly diagnosed, has come back (recurrent), or does not respond to treatment (refractory). ²¹¹At-OKT10-B10 is a monoclonal antibody, called OKT10-B10, linked to a radioactive agent called ²¹¹At. OKT10-B10 attaches to CD38 positive cancer cells in a targeted way and delivers ²¹¹At to kill them. Chemotherapy drugs, such as fludarabine and cyclophosphamide, 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. Radiation therapy such as TBI uses high energy x-rays to kill cancer cells and shrink tumors. Giving ²¹¹At-OKT10-B10 together with chemotherapy and TBI before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.

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.

What data supports the effectiveness of this treatment for multiple myeloma?

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 eliminating minimal residual disease. Additionally, CD38-directed therapies, like daratumumab, have been highly effective in improving survival outcomes for multiple myeloma patients. ^{1 2 3 4 5}

Is the combination of monoclonal antibody, chemotherapy, and radiation safe for stem cell transplant in multiple myeloma?

Research shows that using a monoclonal antibody with radiation and chemotherapy for stem cell transplants in multiple myeloma is generally safe. In one study, no severe side effects were found, and any non-blood-related side effects were manageable. Another study found that using a specific type of radiation with a monoclonal antibody was safe, with only temporary liver issues and no kidney problems. ^{1 6 7 8 9}

What makes this treatment for multiple myeloma unique?

This treatment is unique because it combines a targeted radiation approach using astatine-211 linked to an anti-CD38 monoclonal antibody, which is designed to effectively eliminate minimal residual disease in multiple myeloma by delivering high energy radiation directly to cancer cells. This is combined with chemotherapy and total-body irradiation, followed by a stem cell transplant, offering a comprehensive approach to target and eradicate myeloma cells. ^{1 2 4 10 11}

Research Team

Phuong Vo

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

The α-emitter astatine-211 targeted to CD38 can eradicate multiple myeloma in a disseminated disease model. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells. [2017]

3. China pubmed.ncbi.nlm.nih.gov

[Hemopoietic stem cell transplantation for multiple myeloma-review]. [2016]

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

Evolving transplant options for multiple myeloma: autologous and nonmyeloablative allogenic. [2007]

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

CD38-Directed Therapies for Management of Multiple Myeloma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

90Y-labeled anti-CD45 antibody allogeneic hematopoietic cell transplantation for high-risk multiple myeloma. [2023]

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

Role of stem cell transplantation. [2007]

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

Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation. [2021]

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

Treatment of multiple myeloma. [2021]

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

Radiopharmaceutical therapy of 5T33 murine myeloma by sequential treatment with samarium-153 ethylenediaminetetramethylene phosphonate, melphalan, and bone marrow transplantation. [2019]

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

Mechanism of Action of a New Anti-CD38 Antibody: Enhancing Myeloma Immunotherapy. [2020]