CALGB 50904 - "A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib, and Bendamustine in Patients with Untreated Follicular Lymphoma"

Treatment Plan    (Supplied Drugs:  Ofatumumab, Bortezomib, Bendamustine)

NOTES:

1)  Sites must be credentialed for FDG-PET/CT imaging by the CALGB Imaging Core Laboratory (see Section 10.0).

2)  1 representative from each site with an enrolled pt must participate in a monthly conference call to discuss toxicity (1st 40 pts enrolled).

See protocol for pre-medication & restaging requirements.

ARM A (Cycle = 35 days.  Max 6 cycles.)

INDUCTION

Ofatumumab:  300mg, IV, Day 1, Cycle 1 (immed prior to Bendamustine)

Ofatumumab:  1000mg, IV, Day 1, Cycles 2-6 (immed prior to Bendamustine)

Bendamustine:  90mg/m2, IV over 30-60 mins, Days 1 & 2, each cycle

MAINTENANCE (Starting 8 wks after Cycle 6 Day 1 of INDUCTION in pts w/o disease progression.  Cycle = 56 days.  Max 4 cycles.)

Ofatumumab:  1000mg, IV, Day 1, each cycle

ARM B (Cycle = 35 days.  Max 6 cycles.)

INDUCTION

Ofatumumab:  300mg, IV, Day 1, Cycle 1 (immed prior to Bortezomib & Bendamustine)

Ofatumumab:  1000mg, IV, Day 1, Cycles 2-6 (immed prior to Bortezomib & Bendamustine)

Bendamustine:  90mg/m2, IV over 30-60 mins, Days 1 & 2, each cycle

Bortezomib:  1.6mg/m2, IV over 3-5 secs, Days 1, 8, 15, & 22, each cycle

MAINTENANCE (Starting 8 wks after Cycle 6 Day 1 of INDUCTION in pts w/o disease progression.  Cycle = 56 days.  Max 4 cycles.)

Ofatumumab:  1000mg, IV, Day 1, each cycle (immed prior to Bortezomib)

Bortezomib:  1.6mg/m2, IV over 3-5 secs, Days 1, 8, 15, & 22, each cycle

Eligibility

• Histol-confirmed follicular non-Hodgkin's lymphoma, WHO Grade 1, 2, or 3a (>15 centroblasts/high power field w/centrocytes present).  No BM bxs as sole means of dx, but may be submitted along w/nodal bxs.  No FNAs.  Failure to submit path w/i 60 days of regist is a major protocol violation.

• >1 of the following risk indicators of poor risk disease:

  • >3 risk factors by Follicular Lymphoma Intl Prognostic Index

  • 2 risk factors by Follicular Lymphoma Intl Prognostic Index and >1bulky mass or lymph node >6cm in size

  Follicular Lymphoma Intl Prognostic Index (FLIPI Score) [1, 23]:

  • Age >60

  • >4 involved nodal sites

  • Stg III-IV disease

  • Hgb <12.0mg/dL

  • LDH >ULN

• No prior cytotoxic chemo, RT, immunotherapy, or radioimmunotherapy.

• No corticosteroids except maintenance therapy for non-malig disease or to prevent tx-related Ofatumumab reactions.  Maintenance therapy must not >20mg/day prednisone or equiv.

• Meas disease on PE or imaging.  Non-meas disease alone is not acceptable.  Any tumor mass >1cm is acceptable.  Non-meas lesions include:

  • Bone lesions

  • Leptomeningeal disease

  • Ascites

  • Pleural/pericardial effusions

  • Inflammatory breast disease

  • Lymphangitis cutis/pulmonis

  • BM involvement (involvement by NHL should be noted)

• No known CNS involvement by lymphoma.

• Age >18.

• ECOG perf status 0-2.

• No pregnant or nursing women.  Women of childbearing potential must have negative serum or urine pregnancy test 10-14 days pre-regist.  Men/Women of reproductive potential must use effective contraception throughout study participation.

• HIV-infected pts are eligible if the following are met:  no evidence of co-infection w/Hep B or C; CD4+count >400/ul; no resistant strains of HIV; on anti-HIV therapy w/HIV viral load <50 copies HIV RNA/mL; & no hx of AIDS-defining conditions.

• No active Hep B or C infection (i.e., no positive serology for anti-HBc or anti-HCV antibodies).  HBV seropositive pts (HBsAg+) are eligible if HBV DNA is undetectable at baseline & they are closely monitored for active HBV infection by HBV DNA testing at each tx cycle.

• Granulocytes >1000/ul; platelets >75,000/ul; creat <2.0mg/dL; SGOT & SGPT <2.5x ULN; bili <2x ULN.

• PRESTUDY REQUIREMENTS:

  Within 16 days pre-regist:  All bloodwork, H&P

  Within 28 days pre-regist:  Any radiologic exam, scan of any type, or US used for tumor msmt

  Within 42 days pre-regist:  Any baseline exams used for screening; any radiologic exam, scan of any type, or US of uninvolved organs not utilized for tumor msmt; & BM aspir/bx (bilateral preferred)

  • H&P (physician visit), progress notes, pulse, BP, ht, wt, BSA, perf status, tumor msmts

  • CBC/diff/platelets

  • Serum creat, BUN

  • SGOT, SGPT, alk phos, bili

  • Uric acid, LDH

  • ß2 microglobulin

  • Serum or urine ßHCG (if applicable, 10-14 days pre-regist)

  • HBsAg, HBsAB, HB core antibody

  • HBV DNA testing (only Hep B carriers or prior HBV infection)

  • HCV testing

  • HIV (if applicable)

  • CT/MRI chest/abdomen/pelvis

  • CT/MRI neck (if nodes palpable prior to tx)

  • FDG-PET/CT Scan (baseline - w/i 4 wks of tx initiation)

  • BM aspir & bx (bilat preferred)

  • Histologic Review (FFPE block; must submit w/i 60 days of regist)

  • Sample submission for correlative studies (w/pt's consent)*

  *      10mL whole blood in lavender-top tube & FFPE tissue (only 1 tissue block needed for both histologic confirmation of dx & correlative study). 

• Signed informed consent.