SWOG S0816 - "A Phase II Trial of Response Adapted Therapy of Stage III-IV Hodgkin Lymphoma Using Early Interim FDG-PET Imaging"

NOTE:  Response determinations & tx decisions will be based on Central Review of the FDG-PET & not on scan asmts by local physicians.  KCCOP staff will submit scans electronically via AG Mednet.

Treatment Plan    (Supplied Drug:  None)

HIV-Negative Pts

ABVD x 2 cycles

If PET negative à ABVD x 4

If PET positive à BEACOPP (escalated) x 6

HIV-Positive Pts

ABVD x 2 cycles

If PET negative à ABVD x 4

If PET positive à BEACOPP (standard) x 6

ABVD REGIMEN - (q 28 days x 2 cycles for ALL PTS; q 28 days x 4 additional cycles for PET-NEGATIVE PTS)

Doxorubicin:  25mg/m2, IV, Days 1 & 15

Bleomycin:  10 units/m2, IV, Days 1 & 15

Vinblastine:  6mg/m2, IV, Days 1 & 15

Dacarbazine:  375mg/m2, IV, Days 1 & 15

BEACOPP (Escalated) REGIMEN - (q 21 days x 6 cycles; only pts who are both PET-POSITIVE & HIV-NEGATIVE)

Recommended for 1st dose to be administered in the hospital.

Etoposide:  200mg/m2, IV, Days 1, 2 & 3

Doxorubicin:  35mg/m2, IV, Day 1

Cyclophosphamide:  1250mg/m2, IV, Day 1

Procarbazine:  100mg/m2, PO, Days 1-7

Prednisone:  40mg/m2, PO, Days 1-14

Bleomycin:  10 units/m2, IV, Day 8

Vincristine:  1.4mg/m2 (2mg max), IV, Day 8

Filgrastim (G-CSF):  5mcg/kg/day, SQ, Days 8-14

BEACOPP (Standard) REGIMEN - (q 21 days x 6 cycles; only pts who are both PET-POSITIVE & HIV-POSITIVE)

Recommended for 1st dose to be administered in the hospital.

Etoposide:  100mg/m2, IV, Days 1, 2 & 3

Doxorubicin:  25mg/m2, IV, Day 1

Cyclophosphamide:  650mg/m2, IV, Day 1

Procarbazine:  100mg/m2, PO, Days 1-7

Prednisone:  40mg/m2, PO, Days 1-14

Bleomycin:  10 units/m2, IV, Day 8

Vincristine:  1.4mg/m2 (2mg max), IV, Day 8

Eligibility

• Prev untreated Stg III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte depleted).  No nodular lymphocyte predominant Hodgkin lymphoma.  All histology will be centrally reviewed.

• Path Review:  Adequate sections & paraffin block from orig diagnostic specimen must be available for submission.  If entire block can't be sent, cores or punches are allowed (w/sufficient tissue to establish the architecture & a WHO histologic subtype w/certainty).  Core bxs (especially multiple) MAY be adequate; needle aspirations or cytologies are not.

• Must be offered participation in correlative science studies.

• Age 18-60.

• Must have bidimensionally meas disease assessed w/i 28 days pre-regist.  Non-meas disease (in addition to meas disease) w/i 42 days pre-regist.

• Uni- or bilateral BM bx w/i 42 days pre-regist.

• Diagnostic quality CT chest/abdomen/pelvis AND baseline FDG-PET w/i 28 days pre-regist.  Combined PET/CT scans are required, and older "stand-alone" FDG-PET scans are not adequate for this study.  Low resolution "localization" CTs performed as part of a combined PET/CT are not adequate.  However, if the CT of a PET/CT hybrid is performed w/both PO & IV contrast w/contrast enhancement in the arterial &/or portal venous phase, is at least a 2-slice CT, is acquired w/>80mAs & CTs are obtained w/continguous sections (max 5mm slice thickness), then the pre-tx & any post-therapy PET/CT scan alone will suffice.

• No prior chemo, RT, or antibody therapy for lymphoma.

• Zubrod 0-2.

• Serum ESR, LDH, Hgb, albumin, WBC, & lymphocytes w/i 28 days pre-regist.

• Serum estradiol (women only), testosterone (men only), FSH & LH (both men & women) w/i 60 days pre-regist.

• If hx of HTN or cardiac symptoms, must have MUGA or ECHO w/no significant abnormalities & cardiac ejection fraction >45% w/i 42 days pre-regist.

• No pts sero-positive for Hep B (Hep B surface antigen positive or anti-Hep B core antigen positive) or sero-positive for Hep C (anti-Hep C antibody positive).  Pts who are immune to Hep B (anti-Hep B surface antibody positive) are allowed (i.e., pts immunized against Hep B).

• HIV status must be known pre-regist.  If HIV-positive, must not have multi-drug resistant HIV infection, CD4 counts <150/mcL or other concurrent AIDS-defining conditions.  HIV-positive pts are allowed if CD4 counts >150/mcL at enrollment OR documented CD4 count >250 at any time w/i 8 mos prior to Hodgkin dx (will be analyzed in an independent cohort).

• No significant lung disease w/abnormal LFTs (DLCO >25% below predicted after correction for Hgb) unless attributable to lymphoma.  No requirement for continuous supplemental oxygen therapy.

• No prior solid organ transplant.

• No other prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, adequately treated Stg I or II cancer currently in CR, or any other cancer disease-free >5  yrs.

• No pregnant or nursing women.  Men/Women of reproductive potential must use effective contraception.  "Effective contraception" also includes heterosexual celibacy & surgery intended to prevent pregnancy (hysterectomy, bilat oophorectomy, or bilat tubal ligation).

• PRESTUDY REQUIREMENTS:

  • H&P, wt, perf status

  • Tumor asmt

  • CBC/diff/platelets*

  • Serum creat*

  • Lytes

  • Bili*

  • FSH, LH, & estradiol or testosterone

  • UA*

  • Uric acid*

  • SGOT/SGPT/alk phos*

  • Fertility consultation*

  • Absolute lymphocyte count

  • Albumin

  • LDH

  • Erythrocyte Sedimentation Rate

  • Hep B & C screening

  • BM bx

  • PFTs (including DLCO)

  • Materials for path review**

  • HIV viral load***

  • CD4 count***

  • Serum for correlative studies#

  • Tissue for correlative studies#

  • CT chest (diagnostic quality w/contrast - see specifications above)

  • CT abdomen, pelvis (diagnostic quality w/contrast - see specifications above)

  • FDG-PET/CT scan##

  • Transmit DICOM files to CALGB Imaging Core Lab##

  • ECHO or MUGA (if clinically indicated)

  • EKG

  • CT neck (recommended in pts w/cervical disease)*

  *      Results do not determine eligibility; recommended as good medical practice.

  **    1 H&E section from each block of orig diagnostic specimen (no needle aspirates) & either 12 unstained paraffin slides or a paraffin block from the representative diagnostic specimen.

  ***  Only if HIV positive.

  #      With pt's consent - must be offered.  Serum (10mL in red-top Vacutainer; process per protocol) & tissue (FFPE block from representative diagnostic section OR 12 unstained paraffin slides).  NOTE:  If paraffin block is unavailable or slides were previously submitted for path review, then only 12 additional slides for correlative studies should be submitted.  Ship serum same day as collected (on a cool pack w/dry ice) via overnight delivery (Mon-Thurs only) to:  SWOG Specimen Repository Solid Tumor, Myeloma & Lymphoma Division, Lab #201. 

  ##    All scans (not only pre-study) must be centrally reviewed and NOT assessed by local physicians.  KCCOP will submit scans via AG Mednet.

• Signed informed consent.