Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma
Primary Purpose
Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Hematopoietic Stem Cell Transplantation
Iodine I 131 Monoclonal Antibody BC8
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent B-Cell Non-Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required
- Patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease
- Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
- 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 2.0 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry (patients with disease that does not allow tumor dosimetry will be allowed on study since they still can contribute toward achieving the primary endpoint, but these patients will be given a lower priority over those with evaluable disease)
- Creatinine [Cr] < 2.0
- Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL
- All patients eligible for therapeutic study must have a minimum of >= 4 x10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved and divided into 2 aliquots of at least >= 2 x10^6 CD34/kg each; patients with a history of prior autologous hematopoietic cell transplant (HCT) are only required to have >= 2x10^6 CD34/kg stored
- Patients must have an expected survival of > 60 days and must be free of major infection
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 bone marrow transplant (BMT) (e.g. abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide (DLCO) < 50% predicted, forced expiratory volume in one second (FEV1) < 70% 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 or prior radiation therapy (RT) > 20 Gy to a critical organ within 1 year of enrollment
- Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected PBSC are to be used (patients with cryopreserved stem cells which are negative [=< 0.1% involved] by flow cytometry will also be considered eligible)
- Southwest Oncology Group (SWOG) performance status >= 2.0
- Unable to perform self-care during radiation isolation
- Expected survival if untreated less than 60 days
Sites / Locations
- Fred Hutch/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (iodine I 131 monoclonal antibody B, autologous HCT)
Arm Description
Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant
Dose escalation/de-escalation will be conducted by the "two-stage" approach introduced by Storer. Escalation will continue until a dose-limiting toxicity (DLT) occurs. A DLT will be defined as a therapy-related grade III or IV Bearman (transplant) toxicity. The MTD is estimated to be the dose that is associated with a toxicity rate of 25% (Bearman grade 3-4).
I-131 Activity Administered
Secondary Outcome Measures
Adverse Events
Descriptive statistics will be calculated. DLT will be defined by the Bearman Scale that is designed to address the specific toxicities associated with transplantation.
Overall Survival
Progression-free Survival
number of people with progression free survival
Relapse Rate
Number of relapse
Full Information
NCT ID
NCT00860171
First Posted
March 11, 2009
Last Updated
March 26, 2020
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00860171
Brief Title
Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma
Official Title
A Study Evaluating Escalating Doses of 131I-BC8 (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to lack of funding
Study Start Date
February 2009 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase I trial studies the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given before autologous stem cell transplant in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has returned after a period of improvement or does not respond to treatment. Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving iodine I 131 monoclonal antibody BC8 before an autologous stem cell transplant may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the maximally tolerated dose of 131I-BC8 (anti-cluster of differentiation [CD]45) (iodine I 131 monoclonal antibody BC8) that can be delivered prior to autologous stem cell transplantation for patients with relapsed/refractory B-non-Hodgkin lymphoma (NHL), T-NHL, or 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 assess the radiation dose delivered to tumor sites and normal organs by the above therapy.
III. To evaluate the dose-response relationship of radiation-dose to tumor and clinical response.
IV. To estimate the overall and progression-free survival of the above regimen in such patients.
V. To evaluate the toxicity and tolerability of the above therapy.
VI. To evaluate the feasibility of delivering high-dose 131I-BC8 and autologous stem cell transplantation (ASCT) to B-Cell NHL, T-NHL, and HL patients.
VII. To evaluate the ability to reduce infusion reactions via unlabeled BC8 preinfusion.
OUTLINE: This is a dose-escalation study.
Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.
After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Refractory T-Cell Non-Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
A single site, open label clinical trial.
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (iodine I 131 monoclonal antibody B, autologous HCT)
Arm Type
Experimental
Arm Description
Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 IV on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately 1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Autologous Stem Cell Transplantation
Intervention Description
Autologous stem cells given via central catheter
Intervention Type
Radiation
Intervention Name(s)
Iodine I 131 Monoclonal Antibody BC8
Other Intervention Name(s)
I 131 MOAB BC8, I 131 Monoclonal Antibody BC8, iodine I 131 MOAB BC8, MOAB BC8, iodine I 131, monoclonal antibody BC8, iodine I 131
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant
Description
Dose escalation/de-escalation will be conducted by the "two-stage" approach introduced by Storer. Escalation will continue until a dose-limiting toxicity (DLT) occurs. A DLT will be defined as a therapy-related grade III or IV Bearman (transplant) toxicity. The MTD is estimated to be the dose that is associated with a toxicity rate of 25% (Bearman grade 3-4).
Time Frame
Within 30 days post-transplant
Title
I-131 Activity Administered
Time Frame
At time of I-131 therapy
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Descriptive statistics will be calculated. DLT will be defined by the Bearman Scale that is designed to address the specific toxicities associated with transplantation.
Time Frame
Up to 6 years
Title
Overall Survival
Time Frame
Up to 6 years
Title
Progression-free Survival
Description
number of people with progression free survival
Time Frame
Up to 6 years
Title
Relapse Rate
Description
Number of relapse
Time Frame
Up to 6 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required
Patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease
Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
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 2.0 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry (patients with disease that does not allow tumor dosimetry will be allowed on study since they still can contribute toward achieving the primary endpoint, but these patients will be given a lower priority over those with evaluable disease)
Creatinine [Cr] < 2.0
Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL
All patients eligible for therapeutic study must have a minimum of >= 4 x10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved and divided into 2 aliquots of at least >= 2 x10^6 CD34/kg each; patients with a history of prior autologous hematopoietic cell transplant (HCT) are only required to have >= 2x10^6 CD34/kg stored
Patients must have an expected survival of > 60 days and must be free of major infection
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 bone marrow transplant (BMT) (e.g. abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide (DLCO) < 50% predicted, forced expiratory volume in one second (FEV1) < 70% 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 or prior radiation therapy (RT) > 20 Gy to a critical organ within 1 year of enrollment
Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected PBSC are to be used (patients with cryopreserved stem cells which are negative [=< 0.1% involved] by flow cytometry will also be considered eligible)
Southwest Oncology Group (SWOG) performance status >= 2.0
Unable to perform self-care during radiation isolation
Expected survival if untreated less than 60 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Gopal
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma
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