S0816 Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma

SWOG Cancer Research Network

Status and phase: Completed; Phase 2

Conditions: Nonneoplastic Condition; Lymphoma

Treatments: Biological: filgrastim; Drug: doxorubicin hydrochloride; Drug: dacarbazine; Drug: procarbazine hydrochloride; Drug: ABVD regimen; Drug: prednisone; Drug: vincristine sulfate; Drug: etoposide; Drug: BEACOPP regimen; Drug: vinblastine sulfate; Drug: cyclophosphamide; Biological: bleomycin sulfate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00822120

S0816 (Other Identifier)

CDR0000630501

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. G-CSF may help lessen the side effects in patients receiving chemotherapy. Imaging procedures, such as fludeoxyglucose F 18-PET/CT imaging, may help doctors predict how patients will respond to treatment.

PURPOSE: This phase II trial is studying fludeoxyglucose F 18-PET/CT imaging to see how well it works in assessing response to combination chemotherapy and allow doctors to plan better additional further treatment in treating patients with stage III or stage IV Hodgkin lymphoma.

Full description

OBJECTIVES:

Primary

• To estimate the 2-year progression-free survival (PFS) of HIV-negative patients with stage III-IV Hodgkin lymphoma treated with response-adapted therapy based on fludeoxyglucose F 18 (FDG)-PET imaging after 2 courses of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).
• To estimate the 2-year PFS of patients who are PET-positive after treatment with 2 courses of ABVD and an escalated dose regimen comprising cyclophosphamide, doxorubicin hydrochloride, etoposide, vincristine sulfate, bleomycin, procarbazine hydrochloride, and prednisone (BEACOPP).

Secondary

• To estimate the 2-year overall survival (OS) of patients treated with these regimens.
• To estimate the response rate (i.e., complete and partial responses) in patients treated with these regimens.
• To evaluate the toxicity of these response-adapted regimens.
• To document the feasibility of centralized, real-time review of FDG-PET imaging for U.S. cooperative group studies.
• To prospectively evaluate the overall response rate, complete response rate, PFS, and OS of HIV-positive patients treated with these response-adapted regimens.

OUTLINE: This is a multicenter study.

All patients undergo baseline whole-body fludeoxyglucose F 18 (FDG)-PET/CT imaging before beginning chemotherapy. Patients then receive doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV (ABVD) on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response. Subsequent therapy is based on FDG-PET/CT scan results. Patients are stratified according to FDG-PET positivity (yes vs no). Patients who are FDG-PET-negative continue treatment with ABVD for up to 4 additional courses in the absence of disease progression or unacceptable toxicity. Patients who are FDG-PET-positive are then further stratified according to HIV positivity (yes or no) and receive 1 of the following treatment regimens:

• Escalated-dose BEACOPP chemotherapy: HIV-negative patients receive escalated-dose BEACOPP chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone on days 1-14, and bleomycin IV and vincristine IV on day 8. Patients receive filgrastim (G-CSF) subcutaneously on days 8-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Standard-dose BEACOPP chemotherapy: HIV-positive patients receive standard dose BEACOPP chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone on days 1-14, and bleomycin IV and vincristine IV on day 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Six to eight weeks after completion of chemotherapy, patients undergo a post-treatment FDG-PET/CT scan.

Some patients may undergo bone marrow biopsy at 1 month after the last course of chemotherapy.

After completion of study treatment, patients are followed up periodically for 7 years.

Enrollment: 371 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed classical Hodgkin lymphoma (HL) (i.e., nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted)

  • Previously untreated stage III or IV disease
  • No nodular lymphocyte predominant disease

• Bidimensionally measurable disease

• Adequate biopsy samples from original diagnostic specimen must be available for pathologic review

  • Tissue obtained from core biopsies allowed
  • No tissue obtained from needle aspirations or cytologies

• Must have known HIV status

  • No multi-drug resistant HIV infection, CD4 counts < 150/μL, or other concurrent AIDS-defining conditions in HIV-positive patients
  • HIV-positive patients with CD4 counts ≥ 150/μL at the time of enrollment OR documented CD4 count > 250/μL at any time within 8 months prior to HL diagnosis allowed

• Must have undergone unilateral or bilateral bone marrow biopsy within the past 42 days

• Must have a diagnostic quality CT scan of the chest/abdomen and pelvis AND baseline FDG-PET scan within the past 28 days

  • Combined PET/CT scans required
  • No older "stand-alone" FDG-PET scans
  • No low-resolution "localization" CT scans as part of a combined PET/CT scans

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Serum erythrocyte sedimentation rate, lactate dehydrogenase (LDH), hemoglobin, albumin, white blood cell count (WBC), and lymphocytes measured within the past 28 days

• Serum estradiol (women only), testosterone (men only), follicle stimulating hormone (FSH) and luteinizing hormone (LH) (both men and women) levels must be drawn within 60 days prior to registration

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy

• No significant cardiac abnormalities as assessed by multiple gated acquisition scan (MUGA) or ECHO AND cardiac ejection fraction ≥ 45% in patients with a history of hypertension or cardiac symptoms

• Hepatitis B-negative (i.e., hepatitis B surface antigen-negative or anti-hepatitis B core antigen-negative)

  • Patients immune to or immunized against hepatitis B (i.e., anti-hepatitis B surface antibody-positive) are eligible

• Hepatitis C-negative (i.e., anti-hepatitis C antibody-negative)

• No significant lung disease with abnormal lung function tests (i.e., diffusing capacity of lung for carbon monoxide (DLCO) > 25% below predicted after correction for hemoglobin) unless attributable to lymphoma

• No requirement for continuous supplemental oxygen therapy

• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
• No prior solid organ transplantation

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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371 participants in 4 patient groups

HIV Positive, PET Positive: BEACOPP standard

Experimental group

Description:

Etoposide 100 mg/m2 IV Days 1, 2, 3 Dox 25 mg/m2 IV Day 1 Cyclo 650mg/m2 IV Day 1 Procarb 100 mg/m2 PO Days 1-7 Pred 40 mg/m2 PO Days 1-14 Bleo 10u/m2 IV Day 8 Vincristine 1.4 mg/m2 IV Day 8 Q 21 Days x 6 cycles

Treatment:

Drug: BEACOPP regimen

Drug: etoposide

Drug: vincristine sulfate

Drug: prednisone

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Biological: bleomycin sulfate

Drug: procarbazine hydrochloride

HIV Negative, PET Positive: BEACOPP escalated

Experimental group

Description:

Etoposide 200 mg/m2 IV Days 1, 2, 3 Dox 35 mg/m2 IV Day 1 Cyclo 1,250 mg/m2 IV Day 1 Procarb 100 mg/m2 PO Days 1-7 Pred 40 mg/m2 PO Days 1-14 Bleo 10u/m2 IV Day 8 Vincristine 1.4 mg/m2 IV Day 8 G-CSF 5mcg/kg/day SQ Days 8-14 Q 21 Days x 6 cycles

Treatment:

Drug: BEACOPP regimen

Drug: etoposide

Drug: vincristine sulfate

Drug: prednisone

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Biological: bleomycin sulfate

Biological: filgrastim

Drug: procarbazine hydrochloride

HIV Positive, PET Negative: ABVD

Active Comparator group

Description:

Doxorubicin 25 mg/m2 IV Bleomycin 10u/m2 IV Vinblastine 6mg/m2 IV Dacarbazine 375 mg/m2 IV Days 1, 15 Q 28 Days x 2

Treatment:

Drug: dacarbazine

Drug: vinblastine sulfate

Drug: doxorubicin hydrochloride

Drug: ABVD regimen

Biological: bleomycin sulfate

HIV Negative, PET Negative: ABVD

Active Comparator group

Description:

Doxorubicin 25 mg/m2 IV Bleomycin 10u/m2 IV Vinblastine 6mg/m2 IV Dacarbazine 375 mg/m2 IV Days 1, 15 Q 28 Days x 2

Treatment:

Drug: dacarbazine

Drug: vinblastine sulfate

Drug: doxorubicin hydrochloride

Drug: ABVD regimen

Biological: bleomycin sulfate