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A Randomized, Open-Label, Multi-Center, Phase 2 Study of Zevalin ([90Y]- Ibritumomab Tiuxetan) Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab- Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma

Phase 2
18 Years
Not Enrolling
Non-Hodgkin's Lymphoma

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Trial Information

A Randomized, Open-Label, Multi-Center, Phase 2 Study of Zevalin ([90Y]- Ibritumomab Tiuxetan) Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab- Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma

This multi-center, randomized, open-label study is designed to compare the safety and
efficacy of therapy with Zevalin regimen versus Zevalin and motexafin gadolinium in patients
with rituximab-refractory, low-grade or follicular NHL. Approximately 100 adult patients
will be enrolled in the study (approximately 50 in each group at 15 clinical sites in North

Patients will be screened for eligibility within the 14 days prior to Day 1 of the study.
Once written informed consent has been obtained and patient eligibility has been
established, the patient will be randomized 1:1 to receive either Zevalin or Zevalin and
motexafin gadolinium.

Patients will be assessed for safety at each visit to the study center and for disease
response at Months 3, 6 and 12. An end-of-study-visit will be performed at Month 12.

Disease status will be assessed using positron emission tomography (PET) or PET/CT, and/or
flow cytometry. Disease response will be evaluated in accordance with the standardized
definitions and criteria of the International Working Group Revised Response Criteria for
Malignant Lymphoma. The efficacy endpoints that will be assessed are complete response rate
and overall response rate.

Safety will be assessed by adverse events, physical examinations, vital signs, and clinical
laboratory assessments. Serious adverse events (SAEs) and treatment-emergent adverse
events(TEAEs) will be collected for all patients beginning on Day 1 and continuing through
the end-of study-visit to be performed at Month 12 or withdrawal from study.

Inclusion Criteria:

1. Men or women, at least 18 years of age

2. Histologically-confirmed follicular or indolent, marginal zone and small lymphocytic
B cell non-Hodgkin's lymphoma

3. Progressive disease within 6 months of the end of a rituximab-containing regimen; or
progressive disease at any time following 2 or more prior rituximab-containing
regimens; or progressive disease while on rituximab-containing regimen.

4. At least 1 measurable tumor (> 1.5 cm in the long axis and > 1.0 cm in the short
axis) that has not been irradiated previously or that has increased in size since
previous irradiation

5. A life expectancy of at least 3 months

6. A WHO/ECOG performance status of 0 or 1

7. Adequate hematopoietic function: absolute neutrophil count (ANC) ≥ 1,500 cells/μL,
absolute lymphocyte count (ALC) ≤ 5,000 cells/μL, platelet count ≥ 100,000
cells/μL,hemoglobin ≥ 9 g/dL (may be transfused to maintain this concentration).
Patients who have received pre-phase therapy for purposes of improving performance
status prior to initiating Zevalin are eligible.

8. Adequate liver function: total bilirubin ≤ 2 × upper limit of normal (ULN), AST
(SGOT)and ALT (SGPT) ≤ 2.5 × ULN

9. Creatinine clearance ≥ 60 mL/min/1.73 m2

10. Bone marrow involvement < 25%

11. If men or women of reproductive potential, agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for at least 1
year following treatment with Zevalin

12. Willing and able to provide written Informed Consent and to comply with the
requirements of the study protocol

Exclusion Criteria:

1. Received antineoplastic, experimental, and/or radiation therapy within the 3 weeks
prior to Study Day 1

2. Has not recovered to ≤ Grade 1 from all toxicities related to prior treatments

3. Prior radioimmunotherapy for NHL

4. Autologous stem cell transplant within the 3 months prior to Study Day 1, and/or any
history of allogeneic stem cell transplant with continued allogeneic hematopoiesis

5. Platelet transfusion within the 7 days prior to Study Day 1

6. History of porphyria

7. Grade 2 or higher peripheral neuropathy within the 14 days prior to Study Day 1

8. History of or active central nervous system disease (e.g., primary brain tumor,
seizures not controlled with standard medical therapy, brain metastases)

9. Ongoing, active infection that requires anti infective therapy

10. Clinically significant cardiovascular disease (e.g., unstable angina pectoris,
serious cardiac arrhythmia requiring medication, uncontrolled hypertension,
myocardial infarction, New York Heart Association [NYHA] Class 2 or higher congestive
heart failure, Grade 2 or higher peripheral vascular disease) within the 12 months
prior to Study Day 1

11. History of another clinically significant medical condition, metabolic dysfunction,
physical examination finding, and/or clinical laboratory finding giving reasonable
suspicion of a disease or condition that contraindicates use of an investigational
drug or that might affect interpretation of the results of the study or place the
patient at high risk of treatment complications and/or of noncompliance with the
study procedures

12. Major surgical procedure and/or significant traumatic injury (that which could
interfere with the patient's ability to receive protocol therapy as determined by the
principal investigator) within the 28 days prior to Study Day 1, and/or patient is
anticipated to require a major surgical procedure during the study period

13. Diagnosed with and/or treated for a malignancy other than NHL within the 2 years
prior to Study Day 1, with the exception of complete resection of basal cell
carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, and/or
low-risk prostate cancer after curative therapy from which the patient has been
disease-free for at least 1 year

14. Evidence of a bleeding diathesis and/or a coagulopathy

15. Known HIV infection

16. Known hypersensitivity to drugs with porfyrin-like structures, like Visudyne™.

17. Positive Hepatitis B or C infection: Patient must be tested for hepatitis B surface

18. Pregnant or lactating woman

19. Full dose oral or parenteral anticoagulants within the 10 days prior to Study Day 1,
and/or anticipated full dose oral or parenteral anticoagulant therapy during the
study period(except as required to maintain patency of pre-existing, permanent,
indwelling intravenous catheters) or thrombolytic agents

20. Participated in another clinical study within the 4 weeks prior to Study Day 1

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Response Rate (CR)

Outcome Description:

Primary endpoint is complete response rate within 6 months

Outcome Time Frame:

6 Months

Safety Issue:


Principal Investigator

Andrew M Evens, DO, MSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Massachusetts, Worcester


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

July 2016

Related Keywords:

  • Non-Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Zevalin
  • Motexafin Gadolinium
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell



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