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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Purpose
This phase I trial is studying the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given before autologous stem cell transplant in treating patients with relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma. 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
| Condition | Intervention | 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 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 Splenic Marginal Zone Lymphoma Testicular Lymphoma Waldenström Macroglobulinemia |
Radiation: iodine I 131 monoclonal antibody BC8 Procedure: autologous hematopoietic stem cell transplantation |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Estimation of the maximum tolerated dose of I-131-BC8 that can be delivered prior to transplant [ Time Frame: Within 30 days post-transplant ] [ Designated as safety issue: Yes ]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.
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be calculated.
- Progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier estimates will be calculated.
- Relapse rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Summarized using cumulative incidence estimates combining all patients and will be utilized as a rough guide to the potential benefits and toxicities of this therapy, but we will refrain from formal statistical comparisons with regard to efficacy because of the phase I nature of this trial.
- Incidence of adverse events/toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Descriptive statistics will be calculated. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Dose-limiting toxicity will be defined by the Bearman Scale that is designed to address the specific toxicities associated with transplantation.
| Estimated Enrollment: | 40 |
| Study Start Date: | February 2009 |
| Estimated Primary Completion Date: | February 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (monoclonal antibody, autologous HCT)
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.
|
Radiation: iodine I 131 monoclonal antibody BC8
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Autologous stem cells given via central catheter
|
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 (ASCT) for patients with relapsed/refractory B-non-Hodgkin lymphoma (NHL), T-NHL, or HL.
SECONDARY OBJECTIVES:
I. To optimize the protein dose (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 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 of iodine I 131 monoclonal antibody BC8.
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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)
- Patients must have normal renal function (creatinine [Cr] < 2.0)
- Patients must have normal hepatic function (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) > 20Gy 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
Contacts and Locations| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Ajay K. Gopal 206-288-2037 | |
| Principal Investigator: Ajay K. Gopal | |
| Principal Investigator: | Ajay Gopal | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| Responsible Party: | Gopal, Ajay, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00860171 History of Changes |
| Other Study ID Numbers: | 2238.00, NCI-2010-00128, P01CA044991 |
| Study First Received: | March 11, 2009 |
| Last Updated: | January 23, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Burkitt Lymphoma Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Waldenstrom Macroglobulinemia Mycoses Mycosis Fungoides Sezary Syndrome |
Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoma, Large-Cell, Anaplastic Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Mantle-Cell Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases |
ClinicalTrials.gov processed this record on May 16, 2013