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AzTrials

Plasma Cell MyelomaPhase 1NCT01503242

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

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclosporine and Fludarabine Phosphate in people with Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclosporine and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
9 Jan 2012to 6 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
  • Ability to provide informed consent
  • DONOR: Patients must have an HLA matched donor as well as standard Seattle Cancer Care Alliance (SCCA) and or National Marrow Donor Program (NMDP)/other donor center criteria for PBSC donation
  • DONOR: Donors must consent and be eligible to undergo granulocyte colony-stimulating factor (GCSF) mobilization and PBSC harvest; marrow is not allowed as a source of stem cells on this study

Who cannot join

  • 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)
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  • Prior allogeneic transplant
  • Plasmacytomas > 1 cm in marrow areas measured by magnetic resonance imaging (MRI) or extramedullary plasmacytomas (radiated lesions are exempt from this criteria); patients may receive cytoreductive therapy, including allogeneic stem cell transplant (ASCT) (if high risk) or second ASCT (if failed a prior ASCT) to achieve disease control, but may not receive any cytoreductive therapy within 30 days of the dosimetry infusion and must have bone marrow cellularity meeting inclusion criteria obtained at least 21 days after any cytoreductive/myelosuppressive chemotherapy was last administered
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase I Study of 90Y-BC8-DOTA Monoclonal Antibody, Fludarabine and TBI Followed by HLA-Matched, Allogeneic Peripheral Blood Stem Cell Transplant for the Treatment of Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called allogeneic stem cell transplantation, HSC, HSCT

    Undergo allogeneic peripheral blood stem cell transplantation

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

    Undergo allogeneic peripheral blood stem cell transplantation

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

  • Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8Radiation

    Also called 90Y Anti-CD45 MoAb BC8

    Given IV

Study groups in NCT01503242
Study groupRoleWhat they receive
Treatment (monoclonal antibody, chemo, TBI, transplant)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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%.

    Measured: Up to 180 days

  2. Tissue localization of 111In-BC8-DOTA Ab

    Measured: Up to 72 hours post infusion

Secondary outcomes (4)

  1. Disease response

    Measured: Up to 3 years

  2. Disease-free survival

    Measured: Up to 3 years

  3. Duration of remission

    Measured: Up to 3 years

  4. Overall survival

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2012 (estimated)
  2. Study start9 Jan 2012
  3. Primary completion6 Jun 2017
  4. Study completion6 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01503242
Sponsor's protocol ID
2450.00
Other IDs
NCI-2010-02041, 2450, 2450.00, P30CA015704, R21CA155911
Status last verified
Dec 2019
First submitted
30 Dec 2011
Last updated
9 Dec 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32710011

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclosporine and Fludarabine Phosphate in people with Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of radiation delivered via 90 Y-BC8-DOTA (time frame: Up to 180 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01503242, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.

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