Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin’s Lymphoma

Brief Title

Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

Official Title

A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients With Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma

Brief Summary

      This phase II trial is studying how well giving rituximab together with combination
      chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or
      stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide,
      doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so
      they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium
      ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive
      cancer-killing substances to them without harming normal cells. Combining a monoclonal
      antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more
      cancer cells.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the complete response rate (CR) and functional CR rate in patients with
      previously untreated stage I (with at least 1 risk factor) or stage II CD20+ diffuse large
      cell lymphoma who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

      SECONDARY OBJECTIVES:

      I. To evaluate the time to treatment failure, duration of response, and overall survival in
      these patients who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

      II. To evaluate the toxicity of this therapy. III. To evaluate the toxicity of adding
      involved field radiation therapy > 12 weeks after Zevalin™ for patients with CT+/PET+
      residual masses.

      TERTIARY OBJECTIVES:

      I. To evaluate PET scans pre -and post - R-CHOP/Zevalin™ therapy.

      OUTLINE:

      R-CHOP (rituximab, prednisone, cyclophosphamide, doxorubicin,vincristine): Patients receive
      oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours
      followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day
      1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or
      unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2
      additional courses. Patients achieving a partial response, uncertain CR, or stable disease
      receive 4 additional courses. Patients are evaluated 3 weeks after the last course of
      therapy. Patients with progressive disease go off study.

      Radioimmunotherapy: Beginning no more than 9 weeks after the reevaluation (or 12 weeks after
      the last dose of R-CHOP), patients receive rituximab IV on day 1 followed by indium In 111
      ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab
      IV followed by yttrium 90-Yttrium ibritumomab tiuxetan IV over 10 minutes on day 8.

      Radiotherapy: Patients with residual disease by CT scan or positron emission tomography (PET)
      scan after 12 weeks after radioimmunotherapy undergo conventional involved-field
      radiotherapy.

      Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
      for 3 years, and then annually for 5 years.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.

Secondary Outcome

 3-year Time to Treatment Failure (TTF) Rate

Condition

Contiguous Stage II Adult Diffuse Large Cell Lymphoma

Intervention

rituximab

Study Arms / Comparison Groups

 Treatment

Description:  R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone): Patients receive R-CHOP every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients with progressive disease go off study.
Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8.
Radiation therapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

62

Start Date

December 2004

Completion Date

March 2011

Primary Completion Date

March 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma

          -  Patients must be stage I or II (Modified Ann Arbor staging)

          -  Baseline measurements and evaluations must be obtained within 4 weeks of registration
             to the study; abnormal PET scans will not constitute evaluable disease unless verified
             by CT scan or other appropriate imaging; patients must have at least one objective
             measurable disease parameter (a lesion with at least 1 dimension > 1.5 cm); or if they
             are stage 1

          -  Stage I patients must have at least one of the following risk factors:

               -  Age >= 60 years

               -  Bulky disease (>= 5 cm in at least one dimension)

               -  Elevated Lactate Dehydrogenase (LDH) above institutional upper limit of normal

               -  Eastern Cooperative Oncology Group (ECOG) performance status = 2

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count >= 1500/mm^3 (includes neutrophils and bands)

          -  Platelet count >= 100,000/mm^3

          -  Creatinine < 2.0 mg/dl

          -  Total bilirubin < 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by
             lymphoma); patients with elevated total bilirubin should have a direct bilirubin
             checked; if the direct bilirubin is normal there is no need for a dose reduction

          -  Patients must have left ventricular ejection fraction (LVEF) of > 45%

          -  Patients must be tested for hepatitis B (HBV) surface antigen within 2 weeks of
             registration

               -  NOTE: Patients who test positive will be allowed to participate but must be
                  followed closely for clinical and laboratory signs of active HBV infection and
                  for signs of hepatitis

        Exclusion Criteria:

          -  Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short
             course (=< 14 days prior to registration) of corticosteroids is allowed

          -  Evidence of other malignancy:

               -  Prior chemotherapy or prior radiation therapy for other malignancies

               -  Currently receiving hormone therapy or chemotherapy for another malignancy even
                  if the treatment is being provided in the adjuvant treatment setting, i.e. with
                  no evidence of the original other malignancy

               -  Adjuvant hormonal therapy must have been discontinued > 3 months before entering
                  this study

               -  Patients are eligible if they meet the following conditions: (a) treated
                  carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin
                  cancer; or (c) any other surgically cured malignancy from which the patient has
                  been disease free for at least 3 years

          -  Pregnant or breast feeding, as there would be radiation exposure to the fetus or
             child; a negative pregnancy test is required =< 1 week prior to registration for women
             of childbearing potential (WOCBP). Women of childbearing potential and sexually active
             males must be strongly advised to use an accepted and effective method of
             contraception

          -  Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma

          -  Known HIV infection. The safety of Zevalin™ in this population has not been tested at
             this time

          -  Serious coexisting medical condition or active infection which would compromise the
             ability to deliver standard R-CHOP chemotherapy

          -  Evidence of myelodysplasia on bone marrow aspiration and biopsy
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Thomas Witzig, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00088881

Organization ID

NCI-2012-02957

Secondary IDs

E3402

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Thomas Witzig, Principal Investigator, Eastern Cooperative Oncology Group

Verification Date

April 2017