Radioimmunotherapy for Lymphoma

Project: Research project

Project Details


DESCRIPTION (Provided by applicant): The majority of non-Hodgkin's lymphomas
(NHL) are malignancies of CD2O+ B-lymphocytes. There are approximately 55,000
new cases of NHL each year; and for unexplained reasons, the incidence is
rising. A new form of treatment for B-cell NHL involves the use of rituximab, a
monoclonal antibody that is targeted to the CD2O antigen. Yttrium-90 is a
radioisotope that can be linked to the anti-CD2O antibody to target radiation
to the malignant B-cells. Preliminary studies have established a safe single
dose of Yttrium-90 anti-CD2O antibody (Y2B8) which will produce a tumor
response in 82 percent of patients (pts) with low-grade or follicular NHL. The
primary toxicity of Y2B8 is reversible myelosuppression, which results in
neutropenia and thrombocytopenia and the concomitant increased risk for
infection or bleeding. Indium-111 conjugated to the anti-CD2O antibody (In2B8)
has been developed to predict tumor and normal organ dosimetry. It is
hypothesized that retreatment with Y2B8 delivered 3-4 months after the first
dose will improve the complete remission (CR) rate as well as the duration of
response. The overall objective of this proposal is to develop a safe treatment
strategy that utilizes two sequential doses of Y2B8 separated by 12-16 weeks.
After the maximum tolerated two doses (MTD) of Y2B8 is established, a phase II
trial will be done to learn if the CR rate can be doubled to 50 percent. It is
important to learn the normal organ (including bone marrow) and tumor dosimetry
using In2B8 scanning prior to each dose of Y2B8. Statistical models using the
In2B8 dosimetry results and marrow mass calculations from Tc radiocolloid scans
will be investigated to learn whether marrow toxicity can be predicted. The
results of the In2B8 scans will be correlated with computerized tomography (CT)
and positron emission tomography (PET) scans. CT and PET will be important to
evaluate at the time of the second dose of Y2B8 because many pts have residual
masses detected by CT. It is hypothesized that if the residual masses are
positive by In2B8 or PET scanning that this will represent residual lymphoma
rather than benign scar tissue. Since myelosuppression is the major toxicity of
Y2B8, it is hypothesized that this can be decreased by utilizing prophylactic
colony stimulating factors. After the MTD is established, additional pts will
be treated with prophylactic granulocyte macrophage colony stimulating factor
(GM-CSF) and thrombopoietic growth factor (Interleukin-II, oprelvekin) to learn
whether the myelosuppression can be ameliorated and whether the dose of Y2B8
can be increased. Bone marrow exams will be performed before and after Y2B8 to
evaluate marrow toxicity and effect on marrow cytogenetics. Although it is
unusual for humans to develop an antibody to this antibody (human anti-murine
anti-mouse antibody - HAMA), it is unknown whether pts will have a higher HAMA
rate after two doses of Y2B8 and this will be examined in this protocol. We
anticipate that this novel radioimmunotherapy approach will result in more
effective treatment for pts with NHL.
Effective start/end date4/1/013/31/06


  • Medicine(all)