Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma
18 Years
N/A
Both
Non Hodgkin's Lymphoma, NHL, Aggressive NHL
Trial Information
Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma
The treatment portion of this study consists of study drug administrations each week for
four weeks in a row (a total of 4 treatment days). Patients will then return at intervals up
to 12 weeks for blood samples and for evaluations to see if their disease responded and to
monitor any adverse effects related to treatment. Some blood tests may then need to be
repeated at least a few times and/or until any abnormal findings at earlier evaluations have
resolved. Otherwise, patients will continue to be evaluated every 3 months for two years,
then every 6 months up to 5 years or until the disease worsens. Participation in the study
will end when NHL disease worsens.
Inclusion Criteria:
- Male or female, >18 years old
- Histological diagnosis of CD20+ B-cell NHL, with DLBCL or other aggressive lymphomas
by WHO lymphoma criteria including mantle cell lymphoma and transformed follicular
lymphoma.
- Failed at least one prior standard treatment regimen for NHL
- If DLBCL, ineligible for or refused high-dose chemotherapy with stem cell transplant
- Measurable NHL disease by CT, with at least one lesion >1.5 cm in one dimension
- Adequate performance status (>70 Karnofsky scale, 0-1 ECOG)* with an estimated life
expectancy of at least 6 months
- Laboratory parameters:
- Adequate hematology (Hemoglobin >/= 10 g/dL, ANC >/= 1.5 ´ 109/L, platelets
>/=100 x 109/L) without ongoing transfusional support
- Adequate renal and liver function (creatinine and bilirubin and ALT
- Otherwise,
- 3 months beyond any prior rituximab or veltuzumab treatment, 12 weeks beyond
autologous stem cell transplant and 4 weeks beyond chemotherapy, other experimental
treatments, or any radiation therapy to the index lesion(s).
- Screened for hepatitis B (no time limit) and negative by tests included in NCCN
guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies,
hepatitis B e-antigen).
- Patients of childbearing potential must be willing to practice birth control during
the study until at least 12 weeks after last veltuzumab infusion; women of
childbearing potential must have a negative urine or serum pregnancy test to enter
the study.
- Ability to provide signed, informed consent
Exclusion Criteria:
- Pregnant or lactating women. Women of childbearing potential are required to have a
negative pregnancy test
- NCI CTC Grade 3 or 4 infusion reaction to prior anti-CD20 antibodies (rituximab,
veltuzumab, etc.)
- A known anti-antibody response to prior antiCD20 antibodies (HACA positive, HAHA
positive, etc)
- Prior radioimmunotherapy, including Zevalin or Bexxar.
- Prior high-dose chemotherapy with peripheral blood stem cell transplant.
- Prior therapy with other human or humanized monoclonal antibodies, unless HAHA
tested and negative
- Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of
symptomatic CNS metastases or carcinomatous meningitis.
- Rituximab or veltuzumab resistant, defined as having progressed during or within
6 months of any prior rituximab or veltuzumab treatment.
- Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter
- Bone marrow involvement ≥25%
- Prior external beam radiation therapy to >30% bone marrow.
- Pleural effusion with positive cytology for lymphoma
- Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive
- Known autoimmune disease or presence of autoimmune phenomena.
- Evidence of infection or requiring antibiotics within 7 days.
- Use of systemic corticosteroids within 2 weeks, except low dose regimens
(prednisone, <20 mg/day, or equivalent) which may continue if unchanged.
- Prior malignancies (other than non-melanoma skin cancer or carcinoma in situ of
the cervix) unless disease free for 5 years.
- Prior malignancy with less than a 5-year disease-free interval, excluding
nonmelanoma skin cancers and carcinoma in situ of the cervix.
- Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of
study procedures and follow-up examinations
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety/dose limiting toxicity
Outcome Description:
Patients are closely monitored during and after all infusions, and then at intervals over a 12-week post-treatment evaluation period. Safety evaluations required in all patients include vital signs, physical examination, CBC, serum chemistries, serum immunoglobulins, urinalysis, peripheral blood B-cell levels (immunophenotyping based on CD19), and HAHA (to be analyzed by Sponsor). Adverse events and abnormal laboratories will be graded for toxicity according to NCI CTC v3.0 criteria.
Outcome Time Frame:
12 weeks
Safety Issue:
Yes
Principal Investigator
William Wegener, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Immunomedics, Inc.
Authority:
United States: Food and Drug Administration
Study ID:
IM-T-hA20/90Y-hLL2-01
NCT ID:
NCT01101581
Start Date:
May 2010
Completion Date:
March 2017
Related Keywords:
- Non Hodgkin's Lymphoma
- NHL
- Aggressive NHL
- Diffuse Large cell NHL
- Mantle cell NHL
- Lymphoblastic lymphoma
- Diffuse mixed cell lymphoma
- Diffuse large cell lymphoma
- large noncleaved cell lymphoma
- Aggression
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania 19104 |
| Helen F. Graham Cancer Center | Newark, Delaware 19713 |
| Moffitt Cancer Center | Tampa, Florida 33612 |
| Goshen Center for Cancer Care | Goshen, Indiana 46526 |
| MDACC Orlando | Orlando, Florida 32806 |
| Weill Med College of Cornell Univ/NYH | New York, New York 10021 |
