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Study Summary
No. 2004-0683:.......Lymphoma......Alma Rodriguez [Lymphoma - VP Medical Affairs]......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2004-0683
Study Title:A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin®) for Elderly Patients with Previously Untreated Diffuse Large B-cell Lymphoma
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Physician New Patient Referral
Name:Alma Rodriguez [Lymphoma - VP Medical Affairs]Patients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:N/A
Phase of Study:Phase IIReturn
Visit:
Phase I:R-CHOP will be given in 6 cycles, 21 days apart, with a re-staging
visit after Cycle 4 and
Cycle 6
Phase II: Radioimmunotherapy - pts will return weekly for 13 weeks
Treatment
Agents:
111In-ibritumomab tiuxetan
90Y-ibritumomab tiuxetan
Cyclophosphamide
Darbepoetin alfa
Doxorubicin
G-CSF
Prednisone
Rituximab
Vincristine
Home Care:none
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
none
Description/
Intervention:
The goal of this clinical research study is to learn if treatment with R-CHOP,
filgrastim (Neupogen®) or pegfilgrastim (Neulasta™), darbepoetin alfa (Aranesp®
), and IDEC-Y2B8 (Zevalin®) can help to control high-intermediate and high-risk
diffuse large B-cell lymphoma (DLBCL) in patients who are over 60 years of age.
The safety of this combination treatment will also be studied.
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Study Objectives / Outcomes
The primary efficacy endpoints for this study, evaluating the sequential administration of 6 cycles
of R-CHOP with pegfilgrastim (or filgrastim) and prophylactic Darbepoetin alfa support followed by
90Y-ibritumomab tiuxetan for pts 60 yrs of age or older with previously untreated
high-intermediate or high risk by the age adjusted International Prognostic Index (aaIPI = 2 or 3,
respectively) diffuse large B-cell lymphoma, are to determine progression free survival (PFS) and overall survival (OS).

The primary safety endpoints are to determine the incidence of adverse experiences, hematologic toxicity (white blood cell, Hgb, and platelet nadir; transfusion requirements), cardiac toxicity (the incidence of LV dysfunction and cardiomyopathy) as assessed by echocardiography.

The secondary efficacy endpoints of the study are to determine
1) predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence
2) the treatment response rate for R-CHOP
3) the packed red blood cell transfusion requirements, change in hemoglobin (Hgb) from baseline,
and incidence of anemia (CTC grading) with Prophylactic Darbepoetin alfa support. Hgb
response and correction with darbepoetin alfa is defined as: an increase of >/= 2.0 gm/dl from
baseline and an Hgb >/= 12.0 g/dl, respectively, in the absence of RBC transfusion in the
preceding 21 days.
4) a comparison of baseline FACT-An QOL scores with subsequent evaluations will be performed to correlate the impact of darbepoetin alfa on this QOL measure.
5) the conversion rate to CR with 90Y-ibritumomab tiuxetan for patients with a PR post R-CHOP
6) the effects of sequential R-CHOP and 90Y-ibritumomab tiuxetan on hematopoietic progenitor cells
as determined by stem cell assays performed by Dr. Malcolm Moore's laboratory (at Memorial Sloane Kettering Cancer Center only).
7) Event free survival
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Study Status Information
Study Activation / Registration Date:10/26/2005
IRB Review and Approval Date:11/03/2004
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:65
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must have reached their 60th birthday by the time of enrollment. Patients age 60-65 must be deemed ASCT ineligible at the time of enrollment.

2) Patients must have an initial diagnosis of diffuse large B-cell lymphoma that is confirmed by one of the hematopathologists at the treating institution. Any of the following subtypes of DLBCL, WHO Classification are eligible: centroblastic, immunoblastic, T-cell/histiocyte-rich, lymphomatoid granulomatosis type, anaplastic large B-cell, plasmablastic, mediastinal, or intravascular large B-cell lymphoma. Lymphomas with discordant histology (small cells in the bone marrow) and a DLBCL diagnosis will be eligible for enrollment. All must have initial diagnostic specimen that is CD20-positive.

3) Patients must have at least Ann Arbor Stage II disease and not have disease confined to an involved field radiation port.

4) Patients must have high-intermediate or high-risk DLBCL as defined by an Age-Adjusted IPI (aaIPI) score of 2 or 3 (with 1 point each assigned for a ECOG>1 / KPS less than or equal to 70%, LDH>1x normal, and Stage III or IV)

5) Patients must not have received prior chemotherapy, biologic therapy, or radiation therapy. Patients who have received steroids for less than or equal to 14 consecutive days are eligible. Patients with a history of prior intravenous contrast allergy are permitted to receive steroids as a premedication. However, patients who have already received a single cycle of R-CHOP at standard dosages and otherwise meet all eligibility requirements will be allowed enrollment. These patients will start therapy with cycle number two of R-CHOP provided all pretreatment evaluations meet protocol criteria.

6) Karnofsky performance status of at least 50%.

7) Patients must have a total bilirubin of 2.0 mg/dL or less at the time of study enrollment. The patient may have a bilirubin >2.0 mg/dL if he/she has a history of Gilbert's disease.

8) Patients must have adequate renal function defined as a serum creatinine of 1.5 mg/dL or less at the time of study enrollment. Patients with a serum creatinine of 1.6 mg/dL or greater are still eligible if their 12 or 24-hour creatinine clearance is measured at >50 mL/min. Patients who do not meet either criteria but have renal insufficiency that is believed to be directly caused by lymphomatous involvement of the kidneys or renal collecting system are eligible.

9) Patients must have a cardiac ejection fraction of 50% or greater as determined by echocardiogram.

10) Patients must have HIV antibody test drawn within 4-6 weeks of enrollment; results may be pending provided there is no history of known risk factors or clinical suspicion of HIV.

11) Patients must have no concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy.

12) Patients receiving therapeutic doses of Coumadin may be considered eligible for therapy. Given the potential for thrombocytopenia on this study, the patient's coagulation studies will be closely monitored.

13) Patients must have no prior history of radiotherapy or chemotherapy for a cancer diagnosis (other than lymphoma as listed above) within the last 5 years.

14) Patients must have bi-dimensionally measurable disease at the time of study entry, defined as at least one lymph node greater than or equal to 2.0 x 2.0 cm on physical examination, CT scan, or PET scan.

15) Bone Marrow cellularity at entry must be greater than 15% as determined by a treating institution's hematopathologists or specified as normocellular (~40%) or hyper cellular on the bone marrow biopsy report.

16) Patients must have no known brain or leptomeningeal metastases at the time of study enrollment.

17) Patients must be capable of providing written informed consent.

18) Patients must be screened for Hepatitis B prior to enrollment.

Exclusion Criteria:1) Patients who have not reached their 60th birthday at the time of study entry or who are ages 60-65 and deemed potential future transplant candidates.

2) Patients with any lymphoma subtype other than diffuse large B-cell lymphoma, discordant lymphomas with a DLBCL component are ineligible. Composite lymphomas and patients with primary effusion lymphomas are ineligible.

3) Patients with Stage I or limited Stage II disease (i.e., disease confined to an involved field radiation port).

4) Patients with Low or Low-Intermediate risk disease as defined by aaIPI scores of 0 or 1.

5) Pts who have received prior treatment of any kind for their lymphoma, including chemotherapy, radiation therapy, or biologic therapy. For this trial, corticosteroids will not be considered prior therapy. Pts who have already received a single cycle of R-CHOP at standard dosages and otherwise meet all eligibility requirements will be allowed enrollment. These pts will start therapy with cycle # two of R-CHOP provided all pretreatment evaluations meet protocol criteria. Pts with a history of prior severe intravenous contrast allergy are permitted to receive steroids as a premedication.

6) Karnofsky performance status of less than 50%.

7) Patients with a total bilirubin > 2.0 mg/dL without a history of Gilbert's disease.

8) Patients with a serum creatinine >1.5 mg/dL or creatinine clearance <50 mL/min as a result of medical renal disease.

9) Cardiac ejection fraction of <50% by echocardiogram.

10) HIV-positivity.

11) Concurrent uncontrolled medical problems (including uncontrolled hypertension)

12) Unstable angina pectoris, recent acute myocardial infarction (within 3 months of randomization), or congestive heart failure (> NYHA class II)

13) Subjects with an active seizure disorder. Subjects with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of anti-seizure medication for the previous 5 years.

14) Patients with a history of radiotherapy or chemotherapy for a cancer diagnosis within the last 5 years.

15) Patients with less than 15% bone marrow cellularity as determined by treating institution's hematopathologists.

16) Brain or leptomeningeal metastases at the time of study enrollment

17) Patients incapable of providing written informed consent.

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Links
Registration Number: NCT00058422
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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