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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

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Trial Information

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


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


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)/relapse-free survival

Outcome Time Frame:

2 years after treatment

Safety Issue:

No

Principal Investigator

Amrita Y. Krishnan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Institutional Review Board

Study ID:

07076

NCT ID:

NCT00695409

Start Date:

March 2008

Completion Date:

Related Keywords:

  • Lymphoma
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

City of Hope Medical CenterDuarte, California  91010