CALGB 100104 - "A Phase III Randomized, Double-Blind Study of Maintenance Therapy with CC-5013 or Placebo Following Autologous Stem Cell Transplantation for Multiple Myeloma"

Treatment Plan    (Supplied Drug:  CC-5013/placebo)

1)     REGISTRATION*

2)      Peripheral Blood Stem Cell Transplantation

Mobilization of Autologous Stem Cells:  Target optimal CD34+ cell dose >5 x 10⁶ cells/kg (actual wt)

Autologous PBSC Transplantation:  Approx 2-4 wks after PBSC collection

ACV/VCV:  200-400mg PO, TID, Days -3 through +100 (if hx of herpes simplex infection or seropositivity)

Melphalan:  Either as Single Dose (200mg/m2, IV over 30-60 mins, Day -2 OR Day -1) or as Divided Dose of 100mg/m2/day, IV over 2 days on either Days -3 & -2 OR Days -2 & -1 (200mg/m2 total dose)

PBSCT:  Day 0

Fluconazole:  200mg/day, PO recommended, beginning Day +2 until ANC >500/µL or as clinically indicated

Levofloxacin:  500mg/day, PO (or equiv) recommended, beginning Day +2 until ANC >500/µL or as clinically indicated

G-CSF:  5µg/kg/day, SQ, beginning Day +5 & continuing until ANC >1500/µL for 2 days or >5000/µL for 1 day

TMP/SMX:  1 DS tab, BID, 3x/wk (beginning Day +30 or when ANC >1000/µL through Day +100 [see protocol for alternatives])

3)      RESTAGING (between Day +90 & +100 after transplant and pre-randomiz)

4)      RANDOMIZATION*# (between Day +90 & +100)

5)      MAINTENANCE THERAPY (begins between Day +100 & +110)

CC-5013:  10mg, PO, QD**

Placebo:  10mg, PO, QD**

*     Collect 5-7mL BM aspir at time of orig dx or after max of <2 cycles of induction therapy (if possible), pre-mobilization, pre-randomiz, and at progression or relapse.

**    After 3 mos, dose will be increased to 15mg, PO, QD if lab parameters are met.

#     Pre-randomiz, pts must meet protocol's lab parameters and have no progressive disease. 

Eligibility

• Active multiple myeloma requiring tx (Durie-Salmon Stg >1).  Must have stable disease or be responsive to >2 mos of any induction therapy.  NO smoldering myeloma unless disease has progressed to >Stg 1.

• <12 mos of any prior therapy, including CC-5013 & Thalidomide.

• Must be w/i 12 mos of initiation of induction therapy.

• No prior progression after initial therapy (pts whose therapy is changed due to suboptimal response, intolerance, etc. are eligible if progression criteria is not met).

• No prior perip blood, BM, or solid organ transplant.

• Age >18 & <70.

• ECOG perf status 0-1.

• DLCO >50% predicted w/no symptomatic pulmonary disease.

• LVEF >40% by MUGA or echo.

• No uncontrolled diabetes mellitus.

• No active serious infection.

• No HIV, HBSag, or Hep C positive pts.

• No pregnant or nursing women.  Women of childbearing potential must have negative serum or urine pregnancy test (sensitivity >50 mIU/mL) 10-14 days pre-regist and repeated w/i 24 hrs prior to 1st Lenalidomide dose.  Men/Women of reproductive potential must commit to continued abstinence or begin 2 methods of birth control (1 highly effective method & 1 additional effective method) at same time, beginning >4 wks b/f starting Lenalidomide therapy & x 4 wks after therapy is stopped.

• ANC >1000/µL; platelets >100,000/µL; CrCl >40cc/min (calculate by Cockroft-Gault formula or after 24-hr urine collection); creat & total bili each <2mg/dL; SGOT & alk phos <3x ULN; negative urine or serum HCG (if applicable).

• PRESTUDY REQUIREMENTS: 

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

  Within 42 days pre-regist:  Baseline exams used for screening; any xray, scan, or US of uninvolved organs not used for tumor msmt

  • H&P, progress notes, pulse, BP, ht, wt, BSA

  • Perf status

  • CBC/diff/platelets

  • Chem Profile (to include electrolytes)

  • CrCl

  • Mg

  • TSH, T4

  • b2 microglobulin

  • PFTs, MUGA or Echo

  • Urine or Serum HCG

  • EKG

  • Serum PEP

  • Serum IEP

  • Urine PEP (24 hr)

  • Urine IEP (24 hr)

  • Serum Free Light Chains

  • Quant. Immunoglobulins

  • HBSag, Hep C, HIV

  • CXR (PA & Lat)

  • BM aspir/bx (w/pt's consent)*

  • Cytogenetics

  • Skeletal Survey for Myeloma

  *      5-7mL BM aspir in heparinized (green top) tube.  Ship at ambient temp on same day as obtained to:  Michael Caligiuri, MD; CALGB Leukemia Tissue Bank.  Send via overnight carrier for next day (AM) delivery.  If sent on Friday, check Saturday delivery on invoice.

• Signed informed consent.