Know Cancer

forgot password

Phase II Study for Use of Oral Fludarabine Plus Cyclophosphamide and Rituximab Followed by Zevalin as Front-Line Treatment for Non-Follicular Indolent Lymphomas.

Phase 2
18 Years
70 Years
Not Enrolling
Lymphoma, Non-Hodgkin

Thank you

Trial Information

Phase II Study for Use of Oral Fludarabine Plus Cyclophosphamide and Rituximab Followed by Zevalin as Front-Line Treatment for Non-Follicular Indolent Lymphomas.

Test medication:

- Yttrium-90 (90Y) ibritumomab tiuxetan 0.4 mCi/kg is delivered to patient achieving at
least a partial remission (PR) after chemotherapy as a single dose for patients with
baseline platelet counts>150x10^9/L or 0.3 mCi/kg for patients with baseline platelet
counts of 100 to 149x10^9/L. Rituximab 250mg/sqm is given prior to therapeutic
radiolabeled antibodies.

- Standard dose chemotherapy consisting of cyclophosphamide, fludarabine and rituximab
given every 28 days up to the best response (maximum 6 courses).

- A prophylaxis for pneumocystis carinii as well as for herpes zoster are needed during

Main parameters of activity: activity of Yttrium-90 (90Y) ibritumomab tiuxetan after
cyclophosphamide, fludarabine and rituximab combination.

Inclusion Criteria:

- Patients with a lymphoma refractory to front-line chemotherapy, not including
fludarabine, or in first relapse after chemotherapy not including fludarabine, not
suitable for high-dose chemotherapy supported by auto or allogeneic bone marrow

- Histologically-confirmed small lymphocytic (SLL), lymphoplasmacytic (LPL) and
marginal zone (MZL) lymphomas.

- All prior chemotherapy, including corticosteroids, had to have been completed > 4
weeks before study treatment; < 25% of active bone marrow irradiated previously; no
prior bone marrow transplantation.

- Age: 18-70 years

- ECOG- performance status: 0-2.

- No allergy to mouse proteins.

- CD20 positive B cell lymphoma.

- Ann Arbor stage III or IV disease with bidimensionally measurable disease in at
least one site which has not irradiated, including any adenopathy or mass that could
be measured during a physical examination or that was > 5 cm on a computed
tomographic scan (CT). In the event of splenomegaly or hepatomegaly, extension 5 cm
below the costal margin was considered evidence of measurable disease. Osteoblastic
bone lesions, ascites and pleural effusion are not considered measurable disease.

- Tumor involvement in the marrow<25% before treatment with Zevalin.

- Acceptable hematologic status within one week prior study start: Hb>9g/dL, white
blood count >3x10^9/L, absolute neutrophil count >1.5x10^9/L, platelets >100x10^9/L.

- Written informed consent prior to any study specific screening procedures, with the
understanding that the patient has the right to withdraw from that study at any time,
without prejudice.

- Patients willing and able to comply with the protocol for the duration of the study.

- Patients, if sexually active, must agree to be using effective contraception for the
entire treatment period and for 1 year following treatment. Women, of child-bearing
potential, must have a negative pregnancy test.

Exclusion Criteria:

- Histologies other than those included

- History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the
skin or carcinoma in situ of cervix within the last 5 years.

- Major surgery, other than diagnostic surgery, within the last 4 weeks.

- Presence of malignant ascites or pleural effusions.

- Evidence of CNS involvement. Patients with a history of uncontrolled seizures,
central nervous system disorders or psychiatric disability judged by the investigator
to be clinically significant and adversely affecting compliance to study drugs.

- Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease, cardiac arrhythmias not well controlled with medication, or
myocardial infarction within the last 6 months, NYHA class III or IV heart disease),
abnormal liver function tests, not disease related, within 1 week prior to study
start (serum bilirubin >2 mg/dL; ALAT >2.5 x upper normal limit; alkaline phosphatase
>2.5xupper normal limit), abnormal renal function, not disease related (serum
creatinine >2.0 mg/dL), active opportunistic infections.

- Serum positivity for HIV, HBsAg and HCV except for those with no sign of active viral
replication, assessed by HCV-RNA and HBV-DNA. This latter group of patients can be
enrolled in the study, but they will receive lamivudine prophylaxis and bimonthly
evaluation of HbSAg, HbCAb and HBV-DNA will be provided.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

achievement and duration of complete or partial reduction of lymphnodes six weeks after the end of treatment with zevalin

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Cortelazzo Sergio, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ospedale Centrale di Bolzano (Italy)


Italy: Ministry of Health

Study ID:

EUDRACT 2005-000699-41



Start Date:

August 2005

Completion Date:

August 2009

Related Keywords:

  • Lymphoma, Non-Hodgkin
  • Zevalin
  • Lymphoma, Non-Hodgkin
  • Lymphoma
  • Lymphoma, Non-Hodgkin