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A Study Evaluating Escalating Doses of 131I-BC8 (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies


Phase 1
18 Years
N/A
Open (Enrolling)
Both
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, 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, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Study Evaluating Escalating Doses of 131I-BC8 (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies


PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose of 131I-BC8 (anti-cluster of differentiation
[CD]45) (iodine I 131 monoclonal antibody BC8) that can be delivered prior to autologous
stem cell transplantation (ASCT) for patients with relapsed/refractory B-non-Hodgkin
lymphoma (NHL), T-NHL, or HL.

SECONDARY OBJECTIVES:

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

II. To assess the radiation dose delivered to tumor sites and normal organs by the above
therapy.

III. To evaluate the dose-response relationship of radiation-dose to tumor and clinical
response.

IV. To estimate the overall and progression-free survival of the above regimen in such
patients.

V. To evaluate the toxicity and tolerability of the above therapy. VI. To evaluate the
feasibility of delivering high-dose 131I-BC8 and ASCT to B-Cell NHL, T-NHL, and HL patients.

VII. To evaluate the ability to reduce infusion reactions via unlabeled BC8 preinfusion.

OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.

Patients receive a dosimetric dose of iodine I 131 monoclonal antibody BC8 intravenously
(IV) on day -20 and a therapeutic dose on day -11. Before day -20, patients may also receive
up to 2 additional dosimetric doses of iodine I 131 monoclonal antibody BC8 IV approximately
1-2 weeks apart. Patients then undergo autologous stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and
then annually thereafter.


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

- Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be
enrolled/transplanted in complete remission (CR)/first partial remission (PR1)

- 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 2.0 cm in largest dimension on computed tomography (CT) imaging
for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry
(patients with disease that does not allow tumor dosimetry will be allowed on study
since they still can contribute toward achieving the primary endpoint, but these
patients will be given a lower priority over those with evaluable disease)

- Patients must have normal renal function (creatinine [Cr] < 2.0)

- Patients must have normal hepatic function (bilirubin < 1.5 mg/dL), with the
exception of patients thought to have Gilbert's syndrome, who may have a total
bilirubin above 1.5 mg/dL

- All patients eligible for therapeutic study must have a minimum of >= 4 x10^6 CD34/kg
autologous hematopoietic stem cells harvested and cryopreserved and divided into 2
aliquots of at least >= 2 x10^6 CD34/kg each; patients with a history of prior
autologous hematopoietic cell transplant (HCT) are only required to have >= 2x10^6
CD34/kg stored

- 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 bone
marrow transplant (BMT) (e.g. abnormally decreased cardiac ejection fraction,
diffusion capacity of the lung for carbon monoxide (DLCO) < 50% predicted, forced
expiratory volume in one second (FEV1) < 70% 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 or prior radiation therapy (RT)
> 20Gy to a critical organ within 1 year of enrollment

- Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or
near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected
PBSC are to be used (patients with cryopreserved stem cells which are negative (=<
0.1% involved) by flow cytometry will also be considered eligible)

- Southwest Oncology Group (SWOG) performance status >= 2.0

- Unable to perform self-care during radiation isolation

- Expected survival if untreated less than 60 days

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Estimation of the maximum tolerated dose of I-131-BC8 that can be delivered prior to transplant

Outcome Description:

Dose escalation/de-escalation will be conducted by the "two-stage" approach introduced by Storer. Escalation will continue until a dose-limiting toxicity (DLT) occurs. A DLT will be defined as a therapy-related grade III or IV Bearman (transplant) toxicity.

Outcome Time Frame:

Within 30 days post-transplant

Safety Issue:

Yes

Principal Investigator

Ajay Gopal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2238.00

NCT ID:

NCT00860171

Start Date:

February 2009

Completion Date:

Related Keywords:

  • 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
  • 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
  • Splenic Marginal Zone Lymphoma
  • Testicular Lymphoma
  • Waldenstr√∂m Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • 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

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109