Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00860171
First received: March 11, 2009
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
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 Acute Lymphoblastic Leukemia
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 Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Radiation: iodine I 131 monoclonal antibody BC8
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Estimation of the maximum tolerated dose (MTD) 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. The MTD is estimated to be the dose that is associated with a toxicity rate of 25% (Bearman grade 3-4).


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be calculated.

  • Progression-free survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be calculated.

  • Relapse rate [ Time Frame: Up to 6 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 no formal statistical comparisons with regard to efficacy will be made because of the phase I nature of this trial.

  • Incidence of adverse events/toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be calculated. DLT 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: March 2015 (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:
  • I 131 MOAB BC8
  • I 131 Monoclonal Antibody BC8
  • iodine I 131 MOAB BC8
Procedure: autologous hematopoietic stem cell transplantation
Autologous stem cells given via central catheter
Other: laboratory biomarker analysis
Correlative studies

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 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 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
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)
  • 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) > 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860171

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         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00860171     History of Changes
Other Study ID Numbers: 2238.00, NCI-2010-00128, 2238.00, P30CA015704, P01CA044991
Study First Received: March 11, 2009
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Leukemia, Large Granular Lymphocytic
Lymphoma
Leukemia
Intraocular Lymphoma
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 19, 2014