Phase 1 / 2a Dose Escalation Study in Participants With CLL, SLL, or NHL

This study will identify the highest dose, and assess the safety, of cerdulatinib (PRT062070) that may be given in participants with relapsed / refractory chronic lymphocytic leukemia / small lymphocytic lymphoma or non-hodgkin lymphoma.

Inclusion Criteria

• Inclusion Criteria: Phase 1 Inclusion • Participant at least 18 years of age with histologically confirmed CLL/SLL or B-cell non-Hodgkin lymphoma (diffuse large B-cell lymphoma [DLBCL], FL, mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], lymphoplasmacytic lymphoma). Phase 2a Inclusion - Histological evidence: FL Grade 1-3A, with relapsed or refractory disease; aggressive NHL (aNHL), defined as DLBCL, FL Grade 3B, MCL, and transformed NHL with relapsed disease; CLL/SLL, peripheral T-cell lymphoma (PTCL), or cutaneous T-cell lymphoma (CTCL) (with mycosis fungoides [MF]/Sézary Syndrome [SS]) with relapsed or refractory disease - Received B-cell receptor (BCR) and/or BCL2 inhibitors and were intolerant or had relapsed/refractory disease afterwards - Prior treatment for lymphoid malignancy for progressive /refractory disease - ≥1 prior regimen (minimum 2 cycles) with antibody conjugate/cytotoxic chemotherapy. - Measurable disease defined as: ≥1 lesion that measures ≥1.5 centimeter (cm) single dimension via computed tomography (CT), CT/positive-emission tomography (PET) with nodal or mass lesions; quantifiable circulating tumor cells; and for CTCL: Modified Severity Weighted Assessment Tool (mSWAT) >0 - Ability to provide diagnostic reports General Inclusion - Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 - Hematologic absolute neutrophil count (ANC) >1000/microliter (uL) and platelet >75,000/uL - Creatinine levels as specified by Investigator - Bilirubin <2.0 mg/deciliter [dL] (if Gilberts then <2.5 mg/dL) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <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 within 90 days of Day 1 or active graft-versus-host treatment within 8 weeks of Day 1 - Prior therapy with Spleen Tyrosine Kinase (SYK) inhibitors - Chronic treatment with strong CYP3A4 inhibitor/inducer - Known lymphomatous involvement of the central nervous system (CNS) - Persistent, unresolved National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 ≥Grade 2, previous drug-related toxicity (except alopecia, erectile impotence, hot flashes, libido, neuropathy). - Prior monoclonal antibody (including alemtuzumab), radioimmunoconjugate, antibody drug conjugate, phototherapy, radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any test agent within 3 weeks of Day 1 - For CTCL: (total skin electron beam therapy [TSEBT]) within 12 weeks, or initiation of topical steroid, nitrogen mustard, or topical retinoid within 2 weeks. Stable topical regimen for ≥4 weeks prior to Day 1 allowed. - Known carrier or infection for human immunodeficiency virus (HIV)/hepatitis B or C. If hepatitis C virus (HCV) antibody (ab)+, must be polymerase chain reaction (PCR)- to be eligible. If hepatitis B virus (HBV) ab+, must be hepatitis B surface antigen (HBsAg)- or undetectable HBV deoxyribonucleic acid (DNA) to be eligible. - Active infection requiring systemic treatment, - Significant gastrointestinal (GI) disease, previous major gastric/bowel surgery, difficulty swallowing, or malabsorption syndrome - Major surgery within 4 weeks - Previous malignancies within 2 years 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 pharmacokinetic (PK) parameters conducted in

2 phases:

- Phase 1: Dose-escalation portion, during which participants will be enrolled to receive

a single-agent cerdulatinib at their assigned dose level starting at 15 milligrams (mg)

once daily (QD), administered in increasing doses until the maximum tolerated dose

(MTD)/maximum administered dose (MAD) is identified.

- Phase 2a: Consisting of planned cohorts based on cancer type. The participants will

receive single agent cerdulatinib at a starting dose of 35, 30, or 20 mg twice daily

(BID) for 28-day cycles except for one of the cohorts, the participants will receive

cerdulatinib plus intravenous (IV) rituximab at 375 mg/square meter (m^2) for 28-day

cycles.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Alexion Pharmaceuticals

• Primary ID 13-601
• Secondary IDs NCI-2014-00784
• Clinicaltrials.gov ID NCT01994382