A Phase 1 interventional study of Allogeneic Hematopoietic Stem Cell Transplantation and Cyclosporine in Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, sponsored by Fred Hutchinson Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-12-09.
Sponsored by Fred Hutchinson Cancer Center · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of yttrium Y 90 anti-CD45 monoclonal antibody BC8 when given together with fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant in treating patients with multiple myeloma. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving yttrium Y 90 anti-CD45 monoclonal antibody BC8, fludarabine phosphate, and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening and may be an effective treatment for multiple myeloma.
PRIMARY OBJECTIVES:
I. To assess the tissue localization of 111In-BC8-DOTA antibody therapy (Ab) and establish reproducibly favorable biodistribution.
II. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-BC8-DOTA Ab when combined with fludarabine phosphate (FLU) and 2 Gy total-body irradiation (TBI) as a preparative regimen followed by human leukocyte antigen (HLA)-matched, related or unrelated hematopoietic cell transplant (HCT) for patients with multiple myeloma.
SECONDARY OBJECTIVES:
I. To assess the potential efficacy of this approach, within the limits of a phase I study, by examining disease response, duration of remission, disease free survival (DFS), and overall survival (OS).
OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 (90Y-BC8 Ab).
Patients receive 90Y-BC8 Ab intravenously (IV) on day -12 and fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and allogeneic peripheral blood stem cell transplant on day 0. Patients also receive graft-vs-host disease prophylaxis comprising cyclosporine orally (PO) twice daily (BID) on days -3 to 56 with taper to day 180 or on days -3 to 100 with taper to 180; and mycophenolate mofetil IV or PO BID on days 0-27, or 0-40 with taper to 96.
After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually thereafter.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 15 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.
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Patients must have history of symptomatic myeloma requiring treatment and meet one of the following requirements:
Patients must have a human leukocyte antigen (HLA)-matched related donor or an unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) donation, or bone marrow donation as follows:
Unrelated donor:
Exclusion Criteria:
Patients with the following organ dysfunction:
Patients receive 90Y-BC8 Ab IV on day -12 and fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and allogeneic peripheral blood stem cell transplant on day 0. Patients also receive graft-vs-host disease prophylaxis comprising cyclosporine PO BID on days -3 to 56 with taper to day 180 or on days -3 to 100 with taper to 180; and mycophenolate mofetil IV or PO BID on days 0-27, or 0-40 with taper to 96.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Cyclosporine · Drug: Fludarabine Phosphate · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Radiation: Total-Body Irradiation · Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Undergo allogeneic peripheral blood stem cell transplantation
Also known as: allogeneic stem cell transplantation, HSC, HSCT
Given PO
Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya
Given IV
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Given IV or PO
Also known as: Cellcept, MMF
Undergo allogeneic peripheral blood stem cell transplantation
Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation
Undergo TBI
Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation
Given IV
Also known as: 90Y Anti-CD45 MoAb BC8
MTD of radiation delivered via 90 Y-BC8-DOTA
MTD is defined as the dose that is associated with a true dose-limiting toxicity (DLT) rate of 25%, where a DLT is defined as a grade III/IV regimen-related toxicity (Bearman scale) occurring within 30 days post-transplant. A two-parameter logistic model will be fit to the data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels. Based on this fitted model, the MTD is estimated to be the dose that is associated with a toxicity rate of 25%.
Time frame: Up to 180 days
Tissue localization of 111In-BC8-DOTA Ab
Time frame: Up to 72 hours post infusion
Disease response
Time frame: Up to 3 years
Disease-free survival
Time frame: Up to 3 years
Duration of remission
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
This study is completed, as verified in Dec 2019. You cannot join it, but the record below documents what was studied.
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Fred Hutchinson Cancer Center