ClinicalTrials.gov
ClinicalTrials.gov Menu

Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BEAM Followed By ASCT For Relapsed B-Cell Non-Hodgkin Lymphoma

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.
ClinicalTrials.gov Identifier: NCT00695409
Recruitment Status : Completed
First Posted : June 11, 2008
Results First Posted : July 6, 2018
Last Update Posted : July 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: ASCT Radiation: yttrium Y 90 ibritumomab tiuxetan Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To estimate the 2-year progression free survival.

SECONDARY OBJECTIVES:

II. To estimate the 2-year overall survival.

III. To estimate the 2-year cumulative incidence of progression.

IV. To estimate time to hematopoietic recovery, using absolute neutrophil and platelet engraftment.

V. To estimate incidence of grade 3-4 toxicities by Bearman Scale, Day 0 to Day 100.

VI. To estimate the response rate (CR/PR).

VII. To estimate 100-day treatment related mortality.

VIII. To estimate incidence of myelodysplasia and therapy related acute myeloid leukemia (AML).

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

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Intervention Model: Single Group Assignment
Masking: None (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 Followed by Autologous Stem Cell Transplantation for Poor Risk/Relapsed B-Cell Lymphoma
Actual Study Start Date : March 18, 2008
Actual Primary Completion Date : March 27, 2017
Actual Study Completion Date : March 27, 2017


Arm Intervention/treatment
Experimental: Treatment (RIT, ZBEAM, ASCT)
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: ASCT
Undergo autologous peripheral blood stem cell transplant
Other Name: Autologous Stem Cell Transplantation

Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan




Primary Outcome Measures :
  1. 2-Year Progression-Free Survival [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) to first observation of progressive disease or death due to any cause, whichever comes first, assessed up to 5 years ]
    Progression-free survival (PFS) was defined as time from peripheral stem cell infusion to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]


Secondary Outcome Measures :
  1. 2-Year Overall Survival [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) to death due to any cause, assessed up to 5 years ]
    Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]

  2. 2-Year Cumulative Incidence of Progression [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) to date of first observation of progressive disease or relapsed disease, assessed up to 5 years ]
    The cumulative incidence was estimated after taking into account the competing risk of early death.

  3. Number of Patients With Active Disease at ASCT Achieving CR/PR by Day 100 After ASCT [ Time Frame: Up to Day 100 post-ASCT ]
    Responses are assessed using the Revised Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al. 2007). Complete Response (CR) defined as disappearance of all evidence of disease. Partial Response (PR) defined as regression of measurable disease and no new sites.

  4. Number of Patients With Grade 3-4 Bearman Toxicities. [ Time Frame: From initial of study treatment to Day 100 post-ASCT ]
    Toxicities were recorded using the modified Bearman Scale for non-hematologic adverse events.

  5. 100-Day Treatment-Related Mortality [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) to death due to any couse, assessed up to 5 years ]
    The cumulative incidence was estimated after taking into account the competing risk of relapse post-ASCT.

  6. Time to Neutrophil Recovery [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) till the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL.) ]
    Neutrophil recovery was defined as the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL.

  7. Time to Platelet Recovery [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) till the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions ]
    Platelet recovery was defined as the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions.

  8. Number of Patients With RIT/ZBEAM Developing Therapy Induced MDS and AML [ Time Frame: From peripheral stem cell infusion (Day0 ASCT) to onset of therapy induced MDS/AML, assessed up to 5 years ]
    Patient receiving the full treatment of RIT/ZBEAM developed therapy induced MDS or AML.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00695409


Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Amrita Y. Krishnan, MD City of Hope Medical Center
  Study Documents (Full-Text)

Documents provided by City of Hope Medical Center:

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00695409     History of Changes
Other Study ID Numbers: 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 )
First Posted: June 11, 2008    Key Record Dates
Results First Posted: July 6, 2018
Last Update Posted: July 6, 2018
Last Verified: June 2018

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
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
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Rituximab
Antibodies, Monoclonal
Cytarabine
Melphalan
Etoposide phosphate
Etoposide
Carmustine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antineoplastic Agents, Alkylating