Phase 1 / 2A Dose Escalation Study in CLL, SLL or NHL
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
California
Los Angeles
Palo Alto
San Diego
District of Columbia
Washington
Illinois
Chicago
Kentucky
Lexington
Michigan
Ann Arbor
Missouri
Saint Louis
New Jersey
Hackensack
New York
New York
Ohio
Columbus
Pennsylvania
Philadelphia
South Carolina
Charleston
Texas
Houston
Washington
Seattle
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.
Trial Phase Phase I/II
Trial Type Treatment
Lead Organization
Portola Pharmaceuticals
- Primary ID 13-601
- Secondary IDs NCI-2014-00784
- Clinicaltrials.gov ID NCT01994382