This study will identify the highest dose, and assess the safety, of cerdulatinib (PRT062070)
that may be given in patients with relapsed/refractory chronic lymphocytic leukemia or
This is an open-label, Phase 1/2a, multi dose, multi-center trial of orally administered
cerdulatinib assessing safety, tolerability and PK parameters conducted in 2 phases:
- Phase 1: Dose-escalation portion, during which 43 patients enrolled to receive a
single-agent cerdulatinib at their assigned dose level starting at 15 mg QD,
administered in increasing doses until the MTD/MAD is identified.
- Phase 2a: Consisting of 6 planned cohorts of up to 40 patients each by cancer type. Five
cohorts will receive single agent cerdulatinib at a starting dose of 30 mg BID for
28-day cycles. Cohort 2 receives cerdulatinib plus rituximab IV at 375 mg/m2.
Phase 1 Specific Patient at least 18yrs of age with histologically confirmed CLL/SLL or
B-cell Non-Hodgkin lymphoma (DLBCL, FL, MCL, MZL, lymphoplasmacytic lymphoma).
Phase 2a Inclusion
- Histological evidence: FL Grade 1-3A/iNHL, with relapsed or refractory disease (iNHL
includes LPL/WM, MZL); aNHL, defined as DLBCL, FL Grade 3B, MCL, and transformed NHL
with relapsed disease; CLL/SLL, PTCL, or CTCL (with MF/SS) with relapsed or
- Received BCR and/or BCL2 inhibitors were intolerant or had relapsed/refractory disease
- Prior treatment for lymphoid malignancy for progressive /refractory disease
- ≥ 1 prior regimen (min 2 cycles) with antibody conjugate, cytotoxic chemotherapy, or
TKI alone or in combination.
- Measureable disease defined as: ≥ 1 lesion ≥ 1.5 cm single dimension via CT, CT/PET
with nodal or mass lesions; Quantifiable circulating tumor cells; or for Waldenström's
macroglobulinemia presence of IgM l > 2X ULN; For CTCL: mSWAT > 0
- Ability to provide diagnostic reports
- ECOG Score of 0 or 1.
- Hematologic ANC > 1000/uL and platelet > 75,000/uL,
- Serum creatinine of < 1.5 ULN or calculated CrCl of > 50 mL/min
- Bilirubin < 20.0mg/dL (if Gilberts then < 2.5 mg/dL) and AST/AST < 2.5 ULN
- Richter's syndrome, Burkitt's lymphoma, or Burkitt-like Lymphoma (transformed DLBCL
from Follicular NHL are eligible).
- Prior transplant with stem cell infusion 90 days or active graft-versus-host treatment
within 8 weeks of Day 1.
- Prior therapy with SYK inhibitors.
- Chronic treatment with strong CYP3A4 inhibitor/ inducer, acid reducing agent, Proton
- Known lymphomatous involvement of the CNS.
- Persistent, unresolved NCI CTCAE v4.0 ≥ Grade 2, previous drug-related toxicity
(except alopecia, erectile impotence, hot flashes, libido, neuropathy).
- Prior monoclonal antibody, radioimmunoconjugate, antibody drug conjugate,
phototherapy, radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or
any test agent within 3 weeks or for alemtuzumab 8 weeks of Day 1.
- For CTCL: (TSEBT) within 12 weeks, or initiation of topical steroid, nitrogen mustard,
or topical retinoid within 2 weeks. (Stable topical ≥ 4 weeks prior to Day 1 allowed).
- Known carrier or infection for HIV/Hep B or C. HCV ab+ must be PCR-. HBV ab+ must be
HBsAg- or undetectable DNA
- Active infection requiring systemic treatment,
- Significant GI disease, previous major gastric/bowel surgery, difficulty swallowing or
- Major surgery within 4 weeks
- Previous malignancies within 2 yrs. unless relapse risk is small (< 5%).
- Current use of systemic steroids >20 mg QD prednisone (or equivalent)
- Breastfeeding or pregnant (intention to become) females or participation in other