Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT01678443
Collaborator
National Cancer Institute (NCI) (NIH)
2
Enrollment
1
Location
1
Arm
228.9
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of monoclonal antibody therapy before stem cell transplant in treating patients with relapsed or refractory lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium-90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal 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. Giving radiolabeled monoclonal antibody before a stem cell transplant may be an effective treatment for relapsed or refractory lymphoid malignancies.

Detailed Description

PRIMARY OBJECTIVES:
  1. To estimate the maximally tolerated dose (MTD) of 90Y-BC8-DOTA (anti-cluster of differentiation [CD]45) (yttrium-90 anti-CD45 monoclonal antibody BC8) that can be delivered prior to autologous stem cell transplantation for patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), and Hodgkin lymphoma (HL).
SECONDARY OBJECTIVES:
  1. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in the majority of patients.

  2. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD20 and CD45 targeting.

  3. To describe response rates and remission durations in relapsed B-NHL, T-NHL, and HL following administration of myeloablative doses of 90Y-BC8-DOTA prior to autologous stem cell transplant (ASCT).

  4. To assess the correlation of lymphoma biomarkers with outcomes.

OUTLINE: This is a dose-escalation study of yttrium-90 anti-CD45 monoclonal antibody BC8.

Patients receive indium-111 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -28 and (if necessary) day -21 to evaluate the antibody's biodistribution. Patients then receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies
Actual Study Start Date :
Sep 1, 1999
Actual Primary Completion Date :
Sep 21, 2013
Actual Study Completion Date :
Sep 27, 2018

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8)

Patients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

Biological: indium In 111 anti-CD45 monoclonal antibody BC8
Given IV
Other Names:
  • In 111 MOAB BC8
  • In 111 monoclonal antibody BC8
  • In111 MOAB BC8
  • indium In 111 MOAB BC8
  • Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
    Given IV
    Other Names:
  • 90Y anti-CD45 MAb BC8
  • 90Y anti-CD45 MoAb BC8
  • Procedure: peripheral blood stem cell transplantation
    Undergo autologous peripheral blood stem cell transplant
    Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45 [Up to 30 days after receiving study drug]

      A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.

    Secondary Outcome Measures

    1. Overall Response Rate [Up to 6 years]

    2. Overall Survival [Up to 6 years]

    3. Progression-free Survival [Up to 6 years]

    4. Tumor to Normal Organ Ratios [Up to 6 years]

      Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)

    • Creatinine < 2.0

    • Bilirubin < 1.5 mg/dL

    • All patients eligible for therapeutic study must have a minimum of >= 2 x 10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved

    • Patients must have an expected survival of > 60 days and must be free of major infection

    • Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT tumor dosimetry

    Exclusion Criteria:
    • Circulating human anti-mouse antibody (HAMA), to be determined before each infusion

    • Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab

    • Inability to understand or give an informed consent

    • Lymphoma involving the central nervous system

    • Other serious medical conditions considered to represent contraindications to ASCT (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, acquired immune deficiency syndrome [AIDS], etc.)

    • Known human immunodeficiency virus (HIV) seropositivity

    • Pregnancy or breast feeding

    • Prior allogeneic bone marrow or stem cell transplant

    • Prior autologous bone marrow or stem cell transplant within 1 year of enrollment

    • Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of enrollment

    • Southwest Oncology Group (SWOG) performance status >= 2.0

    • Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved a positron emission tomography (PET)-negative CR following first salvage chemotherapy

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattleWashingtonUnited States98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Ajay Gopal, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01678443
    Other Study ID Numbers:
    • 2361.00
    • NCI-2012-01505
    • 2361.00
    • P01CA044991
    • P30CA015704
    First Posted:
    Sep 5, 2012
    Last Update Posted:
    Apr 2, 2021
    Last Verified:
    Mar 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Period Title: Overall Study
    STARTED2
    COMPLETED2
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Overall Participants2
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52
    (0)
    Sex: Female, Male (Count of Participants)
    Female
    1
    50%
    Male
    1
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    2
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    50%
    White
    1
    50%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    2
    100%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
    DescriptionA DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.
    Time FrameUp to 30 days after receiving study drug

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Measure Participants2
    Count of Participants [Participants]
    0
    0%
    2. Secondary Outcome
    TitleOverall Response Rate
    Description
    Time FrameUp to 6 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Measure Participants2
    Count of Participants [Participants]
    0
    0%
    3. Secondary Outcome
    TitleOverall Survival
    Description
    Time FrameUp to 6 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Measure Participants2
    Mean (Full Range) [days]
    750.5
    4. Secondary Outcome
    TitleProgression-free Survival
    Description
    Time FrameUp to 6 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Measure Participants2
    Count of Participants [Participants]
    0
    0%
    5. Secondary Outcome
    TitleTumor to Normal Organ Ratios
    DescriptionDerived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.
    Time FrameUp to 6 years

    Outcome Measure Data

    Analysis Population Description
    This outcome measure was not done. Only two patients were enrolled before the study was closed early. Tumor to normal organ ratios was not determined due to small sample size.
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    Measure Participants0

    Adverse Events

    Time FrameAEs will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to the investigational product in this study (i.e., the start of the first dosimetry infusion) through day +30 post transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician
    Adverse Event Reporting Description
    Arm/Group TitleTreatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Arm/Group DescriptionPatients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. indium In 111 anti-CD45 monoclonal antibody BC8: Given IV yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant
    All Cause Mortality
    Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Affected / at Risk (%)# Events
    Total0/2 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8)
    Affected / at Risk (%)# Events
    Total2/2 (100%)
    Metabolism and nutrition disorders
    Hyperglycemia1/2 (50%) 1
    Respiratory, thoracic and mediastinal disorders
    Hypoxia1/2 (50%) 1

    Limitations/Caveats

    This study was closed when replaced by a new study adding chemotherapy to this regimen

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAjay K. Gopal, MD
    OrganizationFred Hutchinson Cancer Research Center
    Phone206-288-2037
    Emailagopal@u.washington.edu
    Responsible Party:
    Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01678443
    Other Study ID Numbers:
    • 2361.00
    • NCI-2012-01505
    • 2361.00
    • P01CA044991
    • P30CA015704
    First Posted:
    Sep 5, 2012
    Last Update Posted:
    Apr 2, 2021
    Last Verified:
    Mar 1, 2021