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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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 Summary:

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.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: 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 v4.0 [ Time Frame: Up to 30 days after receiving study drug ]

Original Primary Outcome: MTD of yttrium Y 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: Day -14 ]

Current Secondary Outcome:

  • Overall response rate [ Time Frame: Up to 6 years ]
  • Overall survival [ Time Frame: Up to 6 years ]
  • Progression-free survival [ Time Frame: Up to 6 years ]
  • Tumor to normal organ ratios [ Time Frame: Up to 6 years ]
    Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.


Original Secondary Outcome:

  • Overall response rate [ Time Frame: Up to 6 years ]
  • Overall survival [ Time Frame: Up to 6 years ]
  • Progression-free survival [ Time Frame: Up to 6 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: August 31, 2012
Date Started: December 2012
Date Completion:
Last Updated: December 7, 2015
Last Verified: December 2015