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

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ClinicalTrials.gov Identifier: NCT01678443
Recruitment Status : Active, not recruiting
First Posted : September 5, 2012
Results First Posted : November 9, 2017
Last Update Posted : April 21, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ajay Gopal, Fred Hutchinson Cancer Research Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Waldenström Macroglobulinemia Biological: indium In 111 anti-CD45 monoclonal antibody BC8 Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8 Procedure: peripheral blood stem cell transplantation Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in the majority of patients.

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

III. 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).

IV. 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
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Study Type : Interventional  (Clinical Trial)
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 : September 1, 1999
Actual Primary Completion Date : April 11, 2011
Estimated Study Completion Date : April 10, 2021

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Peripheral T-cell Lymphoma Cutaneous T-cell Lymphoma Follicular Lymphoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Leukemia, T-cell, Chronic Adult T-cell Leukemia/lymphoma Waldenstrom Macroglobulinemia Mycosis Fungoides Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Hodgkin Lymphoma Hairy Cell Leukemia Marginal Zone Lymphoma Extranodal Nasal NK/T Cell Lymphoma Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Sezary Syndrome Burkitt Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Aggressive NK Cell Leukemia Lymphomatoid Granulomatosis T-cell Large Granular Lymphocyte Leukemia

Arms and Interventions
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Arm Intervention/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
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Primary Outcome Measures :
  1. Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45 [ Time Frame: 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 [ Time Frame: Up to 6 years ]
  2. Overall Survival [ Time Frame: Up to 6 years ]
  3. Progression-free Survival [ Time Frame: Up to 6 years ]
  4. Tumor to Normal Organ Ratios [ Time Frame: 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01678443


Locations
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United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
More Information
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Responsible Party: Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01678443    
Other Study ID Numbers: 2361.00
NCI-2012-01505 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2361.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P01CA044991 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: September 5, 2012    Key Record Dates
Results First Posted: November 9, 2017
Last Update Posted: April 21, 2020
Last Verified: April 2020
Additional relevant MeSH terms:
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Mycoses
Burkitt Lymphoma
Lymphoma
Leukemia
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Hodgkin Disease
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
 Plasmablastic Lymphoma
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Intraocular Lymphoma
Leukemia, Large Granular Lymphocytic
Immunoblastic Lymphadenopathy