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 is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00695409
First received: June 10, 2008
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Post-transplant toxicity/complication profile using the modified Bearman Scale and the NCI CTCAE 3.0 scale [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 118
Study Start Date: March 2008
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00695409

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010-3000
Contact: Phyllis Broene    800-826-4673    PBroene@coh.org   
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Amrita Y. Krishnan, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00695409     History of Changes
Other Study ID Numbers: 07076, P01CA030206, P30CA033572, CHNMC-07076, CDR0000597569, NCI-2010-01231
Study First Received: June 10, 2008
Last Updated: August 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Etoposide phosphate
Melphalan
Etoposide
Cytarabine
Carmustine
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014