search
Back to results

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

Primary Purpose

Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
indium In 111 anti-CD45 monoclonal antibody BC8
yttrium Y 90 anti-CD45 monoclonal antibody BC8
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Nasal Type Extranodal NK/T-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; 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 x 10^6 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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8)

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.

Secondary Outcome Measures

Overall Response Rate
Overall Survival
Progression-free Survival
Tumor to Normal Organ Ratios
Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.

Full Information

First Posted
August 31, 2012
Last Updated
March 7, 2021
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01678443
Brief Title
Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to low accrual.
Study Start Date
September 1, 1999 (Actual)
Primary Completion Date
September 21, 2013 (Actual)
Study Completion Date
September 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
indium In 111 anti-CD45 monoclonal antibody BC8
Other Intervention Name(s)
In 111 MOAB BC8, In 111 monoclonal antibody BC8, In111 MOAB BC8, indium In 111 MOAB BC8
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 anti-CD45 monoclonal antibody BC8
Other Intervention Name(s)
90Y anti-CD45 MAb BC8, 90Y anti-CD45 MoAb BC8
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo autologous peripheral blood stem cell transplant
Primary Outcome Measure Information:
Title
Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
Description
A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.
Time Frame
Up to 30 days after receiving study drug
Secondary Outcome Measure Information:
Title
Overall Response Rate
Time Frame
Up to 6 years
Title
Overall Survival
Time Frame
Up to 6 years
Title
Progression-free Survival
Time Frame
Up to 6 years
Title
Tumor to Normal Organ Ratios
Description
Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.
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; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; 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 x 10^6 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Gopal
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/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

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

We'll reach out to this number within 24 hrs