90 Y-BC8-DOTA Monoclonal Antibody, Fludarabine Phosphate, and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT01503242 | Completed Phase 1 DMC

• 5 other identifiers: 2450.00NCI-2010-020412450P30CA015704R21CA155911
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• 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%.

  Up to 180 days

• Tissue localization of 111In-BC8-DOTA Ab

  Up to 72 hours post infusion

Secondary Outcomes (4)

• Disease response

  Up to 3 years

• Disease-free survival

  Up to 3 years

• Duration of remission

  Up to 3 years

• Overall survival

  Up to 3 years

Study Arms (1)

Treatment (monoclonal antibody, chemo, TBI, transplant)

EXPERIMENTAL

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplantation

Also known as: allogeneic stem cell transplantation, HSC, HSCT

Treatment (monoclonal antibody, chemo, TBI, transplant)

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (monoclonal antibody, chemo, TBI, transplant)

Fludarabine Phosphate DRUG

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

Treatment (monoclonal antibody, chemo, TBI, transplant)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Treatment (monoclonal antibody, chemo, TBI, transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

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

Treatment (monoclonal antibody, chemo, TBI, transplant)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (monoclonal antibody, chemo, TBI, transplant)

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 RADIATION

Given IV

Also known as: 90Y Anti-CD45 MoAb BC8

Treatment (monoclonal antibody, chemo, TBI, transplant)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have history of symptomatic myeloma requiring treatment and meet one of the following requirements:
• Have at least 1 high risk feature at diagnosis (including deletion 13 or hypodiploidy by conventional cytogenetics, t(4;14), t(14;16) or deletion 17 by fluorescence in situ hybridization \[FISH\], beta 2 microglobulin \> 3.5, lactate dehydrogenase \[LDH\] greater than 1.5 x upper limit of normal \[ULN\], history of plasma cell leukemia) (prior to chemotherapy); OR
• Have progressive disease on primary therapy with or without prior autologous stem cell transplant; OR
• Have persistent or progressive disease following autologous transplant; it is acceptable for these patients to have a second transplant for disease reduction
• Bone marrow cellularity of \>= 50% of age defined normal values by core biopsy; cellularity must be evaluated within 90 days of the dosimetry infusion and at least 21 days after receiving any cytoreductive/myelosuppressive chemotherapy
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Measured creatinine clearance \> 50 ml/min or estimated creatinine clearance \> 50 ml/min
• For females of childbearing potential, must have a negative pregnancy test
• 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:
• Related donor related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing
• Unrelated donor:
• Matched for HLA-A, B, C, DRB1 DQB1 by high resolution typing; OR
• Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
• Patient and donor pairs homozygous at a mismatched allele, in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A\*0101 and the donor is A\*0102, and this type of mismatch is not allowed
• Ability to provide informed consent

You may not qualify if:

• Patients with the following organ dysfunction:
• Left ventricular ejection fraction \< 35%
• Corrected diffusion capacity of carbon monoxide (DLCO) \< 35% or receiving supplemental continuous oxygen
• Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidences by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
• Pregnant or breast-feeding females
• Circulating antibody against mouse immunoglobulin (HAMA)
• Prior allogeneic transplant
• Prior radiation to maximally tolerated levels to any critical normal organ, or \> 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis)
• Patients who are known to be seropositive for human immunodeficiency virus (HIV)
• Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
• Active central nervous system (CNS) disease at the time of treatment

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Tuazon SA, Sandmaier BM, Gooley TA, Fisher DR, Holmberg LA, Becker PS, Lundberg SJ, Orozco JJ, Gopal AK, Till BG, Coffey DG, Nartea ME, Matesan MC, Pagel JM, Rajendran JG, Press OW, Bensinger WI, Green DJ. 90Y-labeled anti-CD45 antibody allogeneic hematopoietic cell transplantation for high-risk multiple myeloma. Bone Marrow Transplant. 2021 Jan;56(1):202-209. doi: 10.1038/s41409-020-01000-3. Epub 2020 Jul 24.

  PMID: 32710011 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclosporine; Cyclosporins; fludarabine phosphate; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Study Officials

• Damian Green

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2011
• First Posted: January 2, 2012
• Study Start: January 9, 2012
• Primary Completion: June 6, 2017
• Study Completion: December 6, 2019
• Last Updated: December 9, 2019

Record last verified: 2019-12

Locations

US (1)