Recurrent B-Cell Non-Hodgkin LymphomaPhase 1NCT00860171
Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma
A Phase 1 study testing Autologous Hematopoietic Stem Cell Transplantation, Iodine I 131 Monoclonal Antibody BC8 and Laboratory Biomarker Analysis in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation, Iodine I 131 Monoclonal Antibody BC8 and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to 21 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Conditions
- 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
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Iodine I 131 Monoclonal Antibody BC8, Laboratory Biomarker Analysis
- Medical subject headings
- Lymphoma, B-Cell, Hodgkin Disease, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Autologous Stem Cell Transplantation
Autologous stem cells given via central catheter
Iodine I 131 Monoclonal Antibody BC8Radiation
Also called I 131 MOAB BC8, I 131 Monoclonal Antibody BC8, iodine I 131 MOAB BC8, MOAB BC8, iodine I 131
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (iodine I 131 monoclonal antibody B, autologous HCT) | Experimental | 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. Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Radiation: Iodine I 131 Monoclonal Antibody BC8; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Within 30 days post-transplant
I-131 Activity Administered
Measured: At time of I-131 therapy
Secondary outcomes (4)
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.
Measured: Up to 6 years
Overall Survival
Measured: Up to 6 years
Progression-free Survival
number of people with progression free survival
Measured: Up to 6 years
Relapse Rate
Number of relapse
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionMar 2015
- Study completion21 Mar 2020
Why it stopped: Terminated due to lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- A single site, open label clinical trial.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ajay Gopal, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00860171
- Sponsor's protocol ID
- 2238.00
- Other IDs
- NCI-2010-00128, 2238.00, P01CA044991, P30CA015704
- Status last verified
- Aug 2019
- First submitted
- 11 Mar 2009
- Last updated
- 3 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00860171
- Acronym / sponsor ID
- 2238.00
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to lack of funding
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2009
- Primary completion
- Mar 2015 (actual)
- Study completion
- 21 Mar 2020 (actual)
- First posted
- 12 Mar 2009 (estimated)
- Results
- Posted 12 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single site, open label clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Treatment (iodine I 131 monoclonal antibody B, autologous HCT) | Experimental | Procedure: Autologous Hematopoietic Stem Cell Transplantation, Radiation: Iodine I 131 Monoclonal Antibody BC8, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: Autologous Stem Cell TransplantationAutologous stem cells given via central catheter | Procedure or surgery | Treatment (iodine I 131 monoclonal antibody B, autologous HCT) |
| Iodine I 131 Monoclonal Antibody BC8Also: I 131 MOAB BC8, I 131 Monoclonal Antibody BC8, iodine I 131 MOAB BC8, MOAB BC8, iodine I 131Given IV | Radiation | Treatment (iodine I 131 monoclonal antibody B, autologous HCT) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (iodine I 131 monoclonal antibody B, autologous HCT) |
Primary outcome
Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant
Time frame: Within 30 days post-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
Time frame: At time of I-131 therapy
4 secondary outcomes
Adverse Events
Time frame: Up to 6 years
Overall Survival
Time frame: Up to 6 years
Progression-free Survival
Time frame: Up to 6 years
Relapse Rate
Time frame: Up to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ajay Gopal principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous Hematopoietic Stem Cell Transplantation, Iodine I 131 Monoclonal Antibody BC8 and Laboratory Biomarker Analysis in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, 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 8 inclusion and 13 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: stopped early, as of the sponsor's last update on 3 Apr 2020. 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?
Yes. Results are posted in the registry (first posted 12 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of I-131-BC8 That Can be Delivered Prior to Transplant (time frame: Within 30 days post-transplant). 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?
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 3 Apr 2020.