Study of Zevalin Versus Observation in Patients at Least 60 Yrs Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in PET-negative Complete Remission After R-CHOP or R-CHOP-like Therapy

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01510184
First received: January 6, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of Zevalin compared with observation alone in patients who are in PET-negative complete remission after first-line R-CHOP or R-CHOP like therapy.


Condition Intervention Phase
Diffuse Large B-cell Lymphoma
Follicle Center Lymphoma
Drug: Zevalin (ibritumomab tiuxetan)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Open-label, Multicenter, Randomized Study of Sequential Zevalin (Ibritumomab Tiuxetan) Versus Observation in Patients at Least 60 Years of Age With Newly Diagnosed Diffuse Large B-cell Lymphoma in PET-negative Complete Remission After R-CHOP or R-CHOP-like Therapy

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The overall survival rate


Secondary Outcome Measures:
  • OS rate post randomization [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Overall Survival (OS) rate post randomization

  • Progression-free survival [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS)


Enrollment: 81
Study Start Date: April 2012
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Zevalin (ibritumomab tiuxetan)
Day 1: Rituximab 250 mg/m2 intravenous infusion Days 7-9:Rituximab 250 mg/m2 intravenous infusion followed by Y-90-Zevalin 14.8 MBq/kg. In centers where biodistribution imaging is performed Day 1: Rituximab 250 mg/m2 intravenous infusion followed by In-111-Zevalin 185 MBq (5mCi), Days 3-4: Biodistribution imaging Days 7-9: Rituximab 250 mg/m2 intravenous infusion followed by Y-90-Zevalin 14.8 MBq/kg
Drug: Zevalin (ibritumomab tiuxetan)
Day 1: Rituximab 250 mg/m2 intravenous infusion Days 7-9:Rituximab 250 mg/m2 intravenous infusion followed by Y-90-Zevalin 14.8 MBq/kg. In centers where biodistribution imaging is performed Day 1: Rituximab 250 mg/m2 intravenous infusion followed by In-111-Zevalin 185 MBq (5mCi), Days 3-4: Biodistribution imaging Days 7-9: Rituximab 250 mg/m2 intravenous infusion followed by Y-90-Zevalin 14.8 MBq/kg
No Intervention: Observation Arm
Patients randomized to the observation (control) arm will not receive any further anti-lymphoma therapy unless they have a relapse of their disease.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient is 60-years of age or older at time of randomization
  2. Histologically confirmed Ann Arbor stage II, III, or IV DLBCL; or FCL Grade 3B according to the REAL/WHO classification (from initial diagnosis made prior to starting R-CHOP therapy). Results from a pre R-CHOP marrow shall be available for review.
  3. Local pathology review confirming the DLBCL diagnosis and CD20 positivity, and no evidence of DLBCL in bone marrow upon confirmation of CR.
  4. A paraffin block or original slides available for confirmatory pathology review. Patients may be randomized based on the local pathology result.
  5. Age-adjusted IPI of 1, 2, or 3. The age adjusted IPI is defined by one point for LDH > upper limit of normal (ULN); Stage III or IV; and Karnofsky performance status <80% or WHO/ECOG performance status >1.
  6. First-line treatment of DLBCL must have been 6 cycles of standard R-CHOP21, R-CHOP14 or DA-EPOCH-R chemotherapy. Patients who received pre-phase therapy for the purpose of improving performance status prior to initiating R-CHOP are eligible.(See CRF Manual for further clarification).
  7. Complete remission (CR) according to the International Workshop Response Criteria for NHL described by Cheson et al (Appendix 2). after first-line treatment. CT scans of chest, abdomen, pelvis, and neck (if applicable) must have been performed within 6 weeks after the last dose of the last course of chemotherapy. Applicability of the neck CT means that the patient had involvement of the neck region by palpation / physical examination at first diagnosis.
  8. A negative FDG-PET scan confirming complete response, with negative defined as a score of 1-3 on the Deauville 5-point scale (Appendix 3) used to quantify radionucleotide density in PET scans as determined locally (Morschhauser 200735).
  9. Bone marrow cellularity greater than 15%, no evidence of myelodysplasia morphologically and no evidence of involvement with lymphoma either at the pre R-CHOP marrow or on repeat assessment pre-Zevalin. After completing R-chemotherapy, a repeat marrow is required for patients randomized to the Zevalin arm only.
  10. A WHO/ECOG performance status of 0, 1 or 2.
  11. Adequate hematopoietic functions: Absolute neutrophil count (ANC) ≥ 1.0 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 100 x 109/L.
  12. Life expectancy of 6 months or longer
  13. Written informed consent obtained according to local guidelines

Exclusion Criteria:

  1. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy of > 5 years (See CRF Manual for clarification). The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
  2. Prior radioimmunotherapy, including radiation therapy for NHL, or any other NHL therapy.
  3. Presence of primary gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis.
  4. Histological transformation of low-grade NHL.
  5. Active hepatitis B or C. (See CRF completion manual)
  6. Known history of HIV infection.
  7. Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert disease.
  8. Abnormal renal function: serum creatinine > 2.0 × ULN.
  9. Non-recovery from the toxic effects of chemotherapy to < grade 2, or interfering with Zevalin treatment.
  10. Known hypersensitivity to murine or chimeric antibodies or proteins
  11. G-CSF or GM-CSF therapy within 4 weeks prior to Zevalin or observation.
  12. Concurrent severe and/or medically uncontrolled disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study.
  13. Treatment with investigational drugs less than 4 weeks prior to Zevalin or observation.
  14. Major surgery less than 4 weeks prior to Zevalin or start of observation.
  15. Concurrent systemic corticosteroid use for any reason except as premedication in case of known or suspected allergies to contrast media or as premedication for potential side effects of rituximab treatment. Patients on a chronic dose of prednisone for a medical condition (e.g. Asthma or autoimmune disease) less than or equal to 20mg daily, stable for 4 weeks, are permissible.
  16. Unwillingness or inability to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01510184

  Show 93 Study Locations
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Denise Kim, MD Spectrum Pharmaceuticals, Inc
Study Chair: Allen Lee, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01510184     History of Changes
Other Study ID Numbers: SPI-ZEV-11-301
Study First Received: January 6, 2012
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014