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Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma


Phase 2
18 Years
64 Years
Not Enrolling
Both
Lymphoma

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Trial Information

Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma


OBJECTIVES:

- Determine the complete remission rate in patients with low-intermediate-,
high-intermediate-, or high-risk, CD20-positive, diffuse large B-cell lymphoma treated
with induction chemotherapy and rituximab followed by consolidation chemotherapy with
or without rituximab, total body irradiation, and autologous peripheral blood stem cell
transplantation.

- Evaluate positron emission tomography imaging for risk stratification of aggressive
lymphoma by biopsy confirmation of residual lesions at interim restaging in patients
treated with these regimens.

- Determine the safety and toxicity of these regimens in these patients.

OUTLINE: Patients are stratified according to risk (low-intermediate vs high-intermediate or
high).

Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV over
15 minutes, and vincristine IV over 1-2 minutes on day 1; oral prednisone once daily on days
1-5; and filgrastim (G-CSF) subcutaneously (SC) once daily on days 7-11 or PEG-filgrastim
once at least 24 hours after infusion. Patients also receive rituximab IV 2-3 days apart for
a total of 2 doses during the week prior to the first course of chemotherapy and on day 1 of
courses 2-4 of chemotherapy. Treatment repeats every 14 days for a total of 4 courses in the
absence of disease progression or unacceptable toxicity.

After the completion of induction chemotherapy, patients undergo CT scan and positron
emission tomography (PET) scanning. If the PET scan is positive in one or more nodal sites,
a repeat biopsy is performed. Patients with a negative PET scan OR a negative repeat biopsy
(including no evidence of lymphoma on repeat bone marrow biopsy) are assigned to receive
regimen A for consolidation therapy. Patients with a positive repeat biopsy are assigned to
receive regimen B for consolidation therapy.

- Regimen A: Patients receive consolidation chemotherapy comprising etoposide IV over 1
hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on
day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours
after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence
of disease progression or unacceptable toxicity.

- Regimen B: Patients receive consolidation chemotherapy as in regimen A for 3 courses.
Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy.
Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day
5 until the end of leukapheresis). After completion of leukapheresis, patients begin a
regimen of high-dose chemoradiotherapy comprising either total body irradiation twice
daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on
days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and
melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0.
Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood
counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered,
patients receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning
on day 180 in the absence of disease progression.

Patients who receive consolidation therapy on regimen A are followed at 4-6 weeks after
chemotherapy and patients who receive consolidation therapy on regimen B are followed at
90-120 days after transplantation. All patients are followed closely for 5 years and then
annually thereafter.

PROJECTED ACCRUAL: A total of 40-98 patients will be accrued for this study within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed aggressive diffuse large B-cell lymphoma

- CD20-positive disease

- Age-adjusted International Prognostic Index II or III defined by the presence of at
least 1 of the following:

- Karnofsky performance status 10-70%

- Lactate dehydrogenase greater than 200 U/L

- Stage III or IV disease

- Positron emission tomography avid measurable disease

- No CNS involvement

PATIENT CHARACTERISTICS:

Age:

- 18 to 64

Performance status:

- See Disease Characteristics

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count greater than 1,000/mm^3

- Platelet count greater than 50,000/mm^3

Hepatic:

- Bilirubin less than 2.0 mg/dL unless history of Gilbert's disease or pattern
consistent with Gilbert's disease

- Hepatitis B surface antigen and hepatitis C antibody negative

- No chronic, active, or persistent hepatitis

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 60 mL/min

- No chronic renal insufficiency

Cardiovascular:

- Ejection fraction at least 50% by echocardiogram or MUGA scan

- No myocardial infarction within the past 6 months

- No unstable angina

- No cardiac arrhythmias except chronic atrial fibrillation

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- HIV negative

- No other medical illness that would preclude study

- No uncontrolled infection

- No other malignancy within the past 5 years except curatively treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior biologic therapy for malignancy

Chemotherapy:

- No prior chemotherapy for malignancy

Endocrine therapy:

- Prior steroids allowed if received no more than 1 week of therapy

Radiotherapy:

- No prior radiotherapy for malignancy

Surgery:

- No prior surgery for malignancy

Other:

- No other prior therapy for malignancy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Complete remission rate

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Craig Moskowitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

01-142

NCT ID:

NCT00039195

Start Date:

November 2006

Completion Date:

January 2010

Related Keywords:

  • Lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021