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Yttrium Y 90 Ibritumomab Tiuxetan, Rituximab, and High-Dose Combination Chemotherapy Followed By Peripheral Blood Stem Cell Transplant in Treating Patients With Relapsed B-Cell Non-Hodgkin Lymphoma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00695409
First Posted: June 11, 2008
Last Update Posted: March 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
June 10, 2008
June 11, 2008
March 29, 2017
March 18, 2008
March 27, 2017   (Final data collection date for primary outcome measure)
  • Progression-free survival [ Time Frame: Time from transplant to first observation of progressive disease or death due to any cause, whichever comes first, assessed up to 2 years ]
    Estimated using the Kaplan and Meier method. Will consider univariate Cox models for the analysis of potential prognostic factors. Descriptive comparisons with recent historical data from similar patient populations will be made.
  • Incidence adverse events in terms of type and severity and time of onset, using the modified Bearman Scale and then National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 3.0 scale [ Time Frame: Up to 2 years ]
    Descriptive comparisons with recent historical data from similar patient populations will be made
  • Response rate using the Revised Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al) [ Time Frame: Up to 5 years ]
    Response rates will be estimated. Confidence intervals will be established by calculating the exact 95% confidence limits for a binomial parameter.
  • Duration of response (complete response [CR] or partial response [PR]) [ Time Frame: Time from beginning of response (CR or PR) to disease relapse, disease progression, or last disease evaluation if patient in continued CR, PR, assessed up to 5 years ]
  • Post-transplant toxicity/complication profile using the modified Bearman Scale and the NCI CTCAE 3.0 scale [ Time Frame: Up to 2 years ]
    Toxicities observed will be summarized in terms of type, severity, and time of onset. Descriptive comparisons with recent historical data from similar patient populations will be made
  • Incidence of therapy induced myelodysplasia/acute myeloid leukemia [ Time Frame: Up to 5 years ]
    Estimated using the Kaplan and Meier method. Will consider univariate Cox models for the analysis of potential prognostic factors. Descriptive comparisons with recent historical data from similar patient populations will be made.
  • Time to relapse [ Time Frame: Time from RIT based ASCT to date of first observation of progressive disease or relapsed disease, assessed up to 5 years ]
    Estimated using the Kaplan and Meier method. Will consider univariate Cox models for the analysis of potential prognostic factors. Descriptive comparisons with recent historical data from similar patient populations will be made.
  • Overall survival [ Time Frame: Time from transplant to death due to any cause, assessed up to 5 years ]
    Estimated using the Kaplan and Meier method. Will consider univariate Cox models for the analysis of potential prognostic factors. Descriptive comparisons with recent historical data from similar patient populations will be made.
  • Progression-free survival (PFS)/relapse-free survival
  • Overall survival
  • Hematopoietic recovery
  • Early and late pulmonary, cardiac, and hepatic toxicities during the first 100 days post autologous stem cell transplantation (ASCT) and again at 1 year post ASCT as assessed by NCI CTCAE v3.0
  • Response rate
  • Disease progression or relapse
  • Incidence of therapy-induced myelodysplasia and acute myeloid leukemia
Complete list of historical versions of study NCT00695409 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Yttrium Y 90 Ibritumomab Tiuxetan, Rituximab, and High-Dose Combination Chemotherapy Followed By Peripheral Blood Stem Cell Transplant in Treating Patients With Relapsed B-Cell Non-Hodgkin Lymphoma
A Phase II Study of Yttrium-90-Labeled Anti-CD20 Monoclonal Antibody in Combination With High-Dose Beam (BCNU, Etoposide, Cytarabine and Melphalan) Followed by Autologous Stem Cell Transplantation for Patients With Poor Risk/Relapsed B-Cell Lymphoma
This phase II clinical trial studies how well yttrium Y 90 ibritumomab tiuxetan, rituximab, and high-dose chemotherapy followed by peripheral blood stem cell transplant in treating patients with relapsed B-cell non-Hodgkin lymphoma. Monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving monoclonal antibody therapy, radioimmunotherapy (RIT), and high-dose combination chemotherapy before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.

PRIMARY OBJECTIVES: I. To estimate the progression free/relapse free survival and overall survival probabilities among patients with poor risk/relapsed follicular lymphoma (grade 1-3), mantle cell lymphoma, diffuse large B-cell lymphoma, and transformed low-grade lymphoma who undergo radioimmunotherapy (RIT) based autologous stem cell transplant (ASCT).

II. To evaluate hematopoietic recovery, using neutrophil (absolute neutrophil count [ANC] >= 500 x 10^3/ul, ANC >= 1000 x 10^3/ul) and unmaintained platelet (>= 20 x 10^3/ul, >= 100 x 10^3/ul) engraftment as primary criterion, following RIT based autologous stem cell transplant (ASCT).

III. To characterize early and late pulmonary, cardiac and hepatic toxicities during the first 100 days post ASCT and again one year post ASCT.

IV. To evaluate the response rate and the disease progression/relapse rate in patients treated with RIT based ASCT.

V. To evaluate long-term incidence of myelodysplasia and therapy related acute myeloid leukemia (AML) with this new preparative regimen.

VI. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population treated with chemotherapy alone.

VII. To perform exploratory studies on expression of costimulatory molecules before and after RIT based ASCT.

OUTLINE: RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan intravenously (IV) following rituximab IV on day -14.

HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily (BID) and cytarabine IV over 2 hours BID on days -5 to -2; and melphalan IV on day -1.

STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphoma
  • Biological: rituximab
    Given IV
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Drug: carmustine
    Given IV
    Other Names:
    • BCNU
    • BiCNU
    • bis-chloronitrosourea
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: melphalan
    Given IV
    Other Names:
    • Alkeran
    • CB-3025
    • L-PAM
    • L-phenylalanine mustard
    • L-Sarcolysin
  • Procedure: autologous hematopoietic stem cell transplantation
    Undergo autologous peripheral blood stem cell transplant
  • Procedure: peripheral blood stem cell transplantation
    Undergo autologous peripheral blood stem cell transplant
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Radiation: yttrium Y 90 ibritumomab tiuxetan
    Given IV
    Other Names:
    • 90Y ibritumomab tiuxetan
    • IDEC Y2B8
    • Y90 Zevalin
    • Y90-labeled ibritumomab tiuxetan
Experimental: Treatment (radioimmunotherapy, monoclonal, chemo, transplant)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Biological: rituximab
  • Drug: carmustine
  • Drug: cytarabine
  • Drug: etoposide
  • Drug: melphalan
  • Procedure: autologous hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: yttrium Y 90 ibritumomab tiuxetan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
118
March 27, 2017
March 27, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • All patients must have biopsy proven diagnosis of low- and intermediate-grade non-Hodgkin lymphoma (NHL) working formulation B, C,D, E, F, and G; including mantle cell lymphoma; patients with transformed lymphoma are also eligible
  • Demonstrated monoclonal CD20 positive b-cell population in lymph nodes and/or bone marrow
  • Patients must have relapsed after achieving a complete or partial response to prior therapy, have never responded to prior therapy or have poor risk disease
  • Patients with prior bone marrow involvement must have bone marrow aspiration and biopsy within 60 days prior to stem cell collection which shows =< 10% lymphomatous involvement of total cellularity; alternatively, patients with prior bone marrow involvement should have a normal bone marrow study which shows =< 10% lymphomatous involvement within 28 days before salvage chemotherapy
  • Normal renal function test with serum creatinine of < upper limit of normal (ULN), and a creatinine clearance of >= 60 ml/min (measured or calculated)
  • Adequate pulmonary function as measured by forced expiratory volume in 1 second (FEV1) > 60% of predicted measured, or a diffusion capacity of carbon monoxide (DLCO) >= 50% of predicted measured
  • Cardiac ejection fraction of > 50% by echocardiogram or multi gated acquisition (MUGA) scan; the left ventricular ejection fraction (LVEF) from the prestudy echocardiogram (ECHO) or MUGA may be used for eligibility purposes, even if the prestudy stress test indicated a lower LVEF
  • Adequate liver function tests with a bilirubin of =< 1.5 x ULN and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x ULN
  • Negative human immunodeficiency virus antibody
  • Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1; karnofsky performance status (KPS) >= 80
  • No active central nervous system (CNS) disease or prior history of CNS disease
  • Patients must have recovered from last therapy and should be at least four weeks from prior radiation or systemic chemotherapy on the day of administration of Y2B8
  • After the last systemic therapeutic chemotherapy (Cytoxan, administered only for stem cell mobilization is not considered therapeutic) and prior to initiation of high dose treatment, the patient should have a baseline computed tomography (CT) scan and positron emission tomography (PET) scan done; an fluorodeoxyglucose-computed tomography (FDG/CT) scan is sufficient, however, is clinically indicated, an additional diagnostic CT may be ordered; exception: if scans were done and were negative for disease just prior to priming chemotherapy (therapeutic or nontherapeutic) and subsequent stem cell harvest, they do not need to be repeated prior to initiation of high dose treatment

Exclusion Criteria:

  • Presence of human anti-Zevalin antibody (HAZA)
  • Prior radioimmunotherapy
  • Failure to collect adequate number of CD34+ cells >= 3 x 10^6/kg
  • Abnormal cytogenetic study not related to the underlying lymphoma on the bone marrow aspirate sample prior to stem cell collection; if cytogenetics were not performed on the marrow aspirate prior to stem cell collection, cytogenetics on the peripheral blood may be performed
  • Prior bone marrow transplantation
  • Prior malignancy except for:

    • Adequately treated basal cell or squamous cell skin cancer
    • Adequately treated noninvasive carcinoma
    • Other cancer from which the patient has been disease-free for at least five years
  • Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive
  • Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume
  • Patients who have received > 500cGy radiation to the kidneys will be excluded from the study
  • Patients who are pregnant or lactating
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00695409
07076
P01CA030206 ( U.S. NIH Grant/Contract )
P30CA033572 ( U.S. NIH Grant/Contract )
CHNMC-07076
CDR0000597569 ( Registry Identifier: NCI PDQ )
NCI-2010-01231 ( Registry Identifier: NCI CTPR )
Yes
Not Provided
Not Provided
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Amrita Y. Krishnan, MD City of Hope Medical Center
City of Hope Medical Center
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP