Zevalin Before Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of California, Davis
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01811368
First received: March 11, 2013
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

This phase II trial studies how well ibritumomab tiuxetan before donor peripheral blood stem cell transplant works in treating patients with relapsed or refractory non-Hodgkin lymphoma. Giving rituximab, antithymocyte globulin, and total-lymphoid irradiation (TLI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled monoclonal antibodies, such as ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving rituximab, antithymocyte globulin, and TLI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody before a donor peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.


Condition Intervention Phase
Refractory Non Hodgkin Lymphoma
Relapsed Non Hodgkin Lymphoma
Biological: rituximab
Biological: ibritumomab tiuxetan
Biological: anti-thymocyte globulin
Radiation: total nodal irradiation
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Zevalin to Enhance the Efficacy of Non-Myeloablative Allogeneic Transplantation in Patients With Relapsed or Refractory CD20+ Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Response conversion rate (PD/SD to PR and CR) [ Time Frame: Up to 60 days post-transplant ] [ Designated as safety issue: No ]
    Calculated along with 95% confidence intervals (CI). Logistic regression will be used to assess the impact of patient characteristics (e.g., low/high lactate dehydrogenase isoenzyme-3 [LDH] or immunologic correlates) on the response conversion rate.


Secondary Outcome Measures:
  • Time to engraftment/chimerism [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the logrank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes when proper.

  • Rate of acute GVHD [ Time Frame: Up to day 730 ] [ Designated as safety issue: No ]
  • Rate of chronic GVHD [ Time Frame: Up to day 730 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to day 730 ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the logrank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes when proper.

  • EFS [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Comparison of time-to-event endpoints by important subgroups of patients will be made using the logrank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes when proper.

  • Toxicities [ Time Frame: Up to day 730 ] [ Designated as safety issue: Yes ]
    Toxicities as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0


Estimated Enrollment: 20
Study Start Date: March 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

CONDITIONING REGIMEN: Patients receive rituximab IV on days -21 and 14, ibritumomab tiuxetan IV on day -14, TLI on days -11 to -7 and -4 to -1, and antithymocyte globulin IV over 4-6 hours on days -11 to -7. Patients also undergo TLI on days -11 to -7 and -4 to -1.

TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine PO BID or IV on days -3 to 56 with taper to 6 months and mycophenolate mofetil PO BID or IV on days 0-28.

Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Biological: ibritumomab tiuxetan
Given IV
Other Name: Zevalin
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
  • ATGAM
  • lymphocyte immune globulin
  • Thymoglobulin
Radiation: total nodal irradiation
Undergo TLI
Other Names:
  • TLI
  • total lymphoid irradiation
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplant
Drug: cyclosporine
Given PO or IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO or IV
Other Names:
  • Cellcept
  • MMF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To measure the response conversion (progressive disease [PD]/stable disease [SD] to partial response [PR] and complete response [CR]).

SECONDARY OBJECTIVES:

I. To assess the time to engraftment/chimerism. II. To assess the rate of acute and chronic graft-versus-host disease (GVHD). III. To assess toxicity. IV. To determine the overall survival. V. To investigate immune functional and phenotypic analysis. VI. To measure two year event free survival (EFS).

OUTLINE:

CONDITIONING REGIMEN: Patients receive rituximab intravenously (IV) on days -21 and 14, ibritumomab tiuxetan IV on day -14, TLI on days -11 to -7 and -4 to -1, and antithymocyte globulin IV over 4-6 hours on days -11 to -7. Patients also undergo TLI on days -11 to -7 and -4 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) twice daily (BID) or IV on days -3 to 56 with taper to 6 months and mycophenolate mofetil PO BID or IV on days 0-28.

After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   19 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed relapsed cluster of differentiation (CD)20+ non-Hodgkin's lymphoma (NHL) (included in this category are follicular grade I, II, III, marginal zone, mantle cell, diffuse large B cell, small lymphocytic lymphoma) and CD20+ Hodgkin's disease for which standard curative therapy does not exist or is no longer effective
  • Patients must have had at least one prior chemotherapeutic regimen; steroids alone and local radiation do not count as regimens; radiotherapy must have been completed at least 4 weeks prior to entry into the study; Rituxan alone does not count as a regimen; however, Bexxar or Zevalin (ibritumomab tiuxetan) do and patients must have completed radioimmunotherapy (RIT) > 12 months prior to enrollment
  • Karnofsky performance status of ≥ 60%
  • Life expectancy of greater than 3 months
  • Total bilirubin within institutional normal limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Blood counts no restrictions
  • Patients who had anything less than a CR (PR, SD or progressive disease) to their last salvage regimen
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients fit for non-myeloablative transplantation or best treatment that have an available matched (9/10 or better) related or unrelated donor
  • Patients who are considered rituximab refractory (defined as progression within 6 months of their last rituximab-containing regimen)

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, rituximab within three months (unless there is evidence of progression), or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include the use of steroids which may continue until two days prior to enrollment
  • Patients may not be receiving any other investigational agents
  • Failure to obtain insurance/payment authorization for Zevalin, unless the subject agrees to cover the cost
  • Patients with known active brain metastases, other neurological disorders/dysfunction or a history of seizure disorder, or other neurological dysfunction should be excluded from this clinical trial because of their poor prognosis
  • Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month
  • Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure; left ventricular ejection fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is < 30%
  • Patients requiring supplementary continuous oxygen; diffusion capacity of the lung of carbon monoxide (DLCO) is not required to be measured, however if it is measured, patient is excluded if DLCO < 35%
  • Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension
  • Patients with any of the following liver function abnormalities will be excluded:

    • Fulminant liver failure
    • Cirrhosis with evidence of portal hypertension or bridging fibrosis
    • Alcoholic hepatitis
    • Esophageal varices
    • A history of bleeding esophageal varices
    • Hepatic encephalopathy
    • Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
    • Ascites related to portal hypertension
    • Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
    • Symptomatic biliary disease
  • Pregnant women are excluded from this study
  • Human immunodeficiency virus (HIV)-positive patients
  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: NCT01811368

Locations
United States, California
UC Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Joseph M. Tuscano    916-734-3089    joseph.tuscano@ucdmc.ucdavis.edu   
Principal Investigator: Joseph M. Tuscano         
Sponsors and Collaborators
University of California, Davis
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Joseph Tuscano UC Davis Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01811368     History of Changes
Other Study ID Numbers: UCDCC#233, NCI-2012-02753
Study First Received: March 11, 2013
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Mycophenolic Acid
Antilymphocyte Serum
Mycophenolate mofetil
Cyclosporins
Cyclosporine
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 30, 2014