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

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Follicular Lymphoma (FL/Indolent NHL); Aggressive NHL (a NHL); Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL); T-cell Lymphoma (PTCL and CTCL); B-cell Non Hodgkin Lymphoma (NHL)

Treatments: Drug: Cerdulatinib; Biological: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01994382

13-601

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 260 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

260 participants in 3 patient groups

Phase 1 Cerdulatinib

Experimental group

Description:

During Phase 1, participants will receive oral cerdulatinib on Day 1 and then starting on Day 4 at doses of 15 mg up to 100 mg QD or oral cerdulatinib at doses of 15 mg up to 45 mg BID in 28-day cycles (except Cohort 1 will have a 21-day cycle starting on Day 1) for up to 10 cycles.

Treatment:

Drug: Cerdulatinib

Phase 2a Cerdulatinib

Experimental group

Description:

During Phase 2a, participants in cohorts based on cancer type will receive oral cerdulatinib at starting doses of 35, 30, or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib can be reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval.

Treatment:

Drug: Cerdulatinib

Phase 2a Cerdulatinib plus Rituximab

Experimental group

Description:

During Phase 2a, participants in this cohort will receive oral cerdulatinib at their applicable dose and an IV injection of rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, and 10.

Treatment:

Biological: Rituximab

Drug: Cerdulatinib