Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
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Purpose
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 | 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 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 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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 |
- MTD of yttrium-90 anti-CD45 monoclonal antibody BC8 before stem cell transplant defined as dose-limiting toxicity rate of 25% graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 30 days after receiving study drug ] [ Designated as safety issue: Yes ]
- Overall response rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 45 |
| Study Start Date: | December 2012 |
| Estimated Primary Completion Date: | June 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
Given IV
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
|
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.
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; 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 x10^6 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| 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
| ClinicalTrials.gov Identifier: | NCT01678443 History of Changes |
| Other Study ID Numbers: | 2361.00, NCI-2012-01505, P01CA044991 |
| Study First Received: | August 31, 2012 |
| Last Updated: | March 27, 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, Hairy 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 Leukemia, Large Granular Lymphocytic Epstein-Barr Virus Infections Herpesviridae Infections |
ClinicalTrials.gov processed this record on May 23, 2013