Phase 1 / 2A Dose Escalation Study in CLL, SLL or NHL

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 non-hodgkin lymphoma

Inclusion Criteria

• Inclusion Criteria: 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 refractory. - Received BCR and/or BCL2 inhibitors were intolerant or had relapsed/refractory disease afterwards. - 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 General Inclusion - 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 Exclusion Criteria: - 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 pump inhibitors - 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 malabsorption syndrome. - 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 clinical trials

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.

Lead Organization
Portola Pharmaceuticals