Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01921387
First received: August 9, 2013
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

This phase I/II trial studies the side effects and the best dose of radiolabeled monoclonal antibody when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with high-risk lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy before a stem transplant stops the growth of cancer cells by stopping them from dividing or killing them. Stem cells collected from the patient's blood are then returned to the patient to replace the blood-forming cells that were destroyed by the radiolabeled monoclonal antibody and chemotherapy.


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
Noncutaneous Extranodal 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: yttrium Y 90 anti-CD45 monoclonal antibody BC8
Drug: carmustine
Drug: etoposide
Drug: cytarabine
Drug: melphalan
Procedure: peripheral blood stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Lymphoid Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD of yttrium Y 90 anti-CD45 monoclonal antibody BC8, defined as the dose that is associated with a true dose-limiting toxicity (DLT) rate of 25% [ Time Frame: Within 30 days post-transplant ] [ Designated as safety issue: Yes ]
    DLT is defined as a therapy-related grade III or IV Bearman (transplant) toxicity.

  • Progression-free survival following ASCT [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The lowest antibody (yttrium Y 90 anti-CD45 monoclonal antibody BC8) dose (mg/kg) that is consistent with a favorable biodistribution rate >= 80% in lymphoma patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A favorable biodistribution in a given patient will be defined by the target tissue receiving higher radiation dose per unit-administered activity (cGy/mCi) relative to all critical normal organs (lung, liver, kidney, etc.).

  • Estimated dose to tumor sites based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 anti-CD45 monoclonal antibody BC8 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: October 2013
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)
Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0.
Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
Given IV
Other Names:
  • 90Y anti-CD45 MAb BC8
  • 90Y anti-CD45 MoAb BC8
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: peripheral blood stem cell transplantation
Undergo autologous PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplant
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum-tolerated dose (MTD) of 90Y-BC8-DOTA (yttrium Y 90 anti-CD45 monoclonal antibody BC8) (anti-cluster of differentiation [CD] 45) that can be delivered prior to myeloablative carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplant (ASCT) for patients with high-risk B-non-Hodgkin lymphoma (NHL), T-NHL, and Hodgkin lymphoma (HL).

II. To evaluate the efficacy of 90Y-BC8-DOTA when administered at the estimated MTD prior to BEAM chemotherapy and ASCT for patients with high-risk B-NHL, T-NHL, and HL compared to historical controls treated with BEAM alone.

SECONDARY OBJECTIVES:

I. To describe the toxicity observed from the addition of 90Y-BC8-DOTA to BEAM.

II. To optimize the protein dose (Ab) to deliver a favorable biodistribution in the majority of patients.

III. To describe response rates and overall survival of patients with high-risk B-NHL, T-NHL, and HL following administration of 90Y-BC8-DOTA plus BEAM prior to ASCT.

IV. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD45 targeting.

V. To assess the correlation of lymphoma biomarkers with outcomes.

VI. To evaluate the effects of nodal-targeted irradiation by 90Y-BC8-DOTA on immune reconstitution following ASCT.

OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 followed by a phase II study.

Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours twice daily (BID) on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplant 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
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 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

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 carbon monoxide [DLCO] < 50% predicted, etc.)
  • Known human immunodeficiency virus (HIV) seropositivity
  • Pregnancy or breast feeding
  • Prior autologous or allogeneic bone marrow or stem cell transplant
  • Prior radiation therapy (RT) > 20 gray (Gy) to a critical organ within 1 year of enrollment
  • Southwestern Oncology Group (SWOG) performance status >= 2.0
  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: NCT01921387

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: NCT01921387     History of Changes
Other Study ID Numbers: 2728.00, NCI-2013-01378, 2728.00, P01CA044991, P30CA015704
Study First Received: August 9, 2013
Last Updated: July 3, 2014
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, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
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
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
Intraocular Lymphoma
Lymphoma, Mantle-Cell
Leukemia, Large Granular Lymphocytic

ClinicalTrials.gov processed this record on August 28, 2014