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

NCT ID: NCT01994382

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-30
• Study Completion Date: 2020-12-15

Brief Summary

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.

Detailed 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.

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)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Cerdulatinib

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.

Group Type: EXPERIMENTAL

Cerdulatinib

Intervention Type: DRUG

Oral capsule

Phase 2a Cerdulatinib

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.

Group Type: EXPERIMENTAL

Cerdulatinib

Intervention Type: DRUG

Oral capsule

Phase 2a Cerdulatinib plus Rituximab

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.

Group Type: EXPERIMENTAL

Cerdulatinib

Intervention Type: DRUG

Oral capsule

Rituximab

Intervention Type: BIOLOGICAL

IV infusion

Interventions

Cerdulatinib

Oral capsule

Intervention Type: DRUG

Rituximab

IV infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

PRT062070; ALXN2075; Rituxan®; Truxima®; Rixathon®; Ruxience®; MabThera®

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Portola Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Portola Study Director

Role: STUDY_DIRECTOR

Portola Pharmaceuticals

Locations

Huntsville, Alabama, United States

Gilbert, Arizona, United States

Los Angeles, California, United States

Palo Alto, California, United States

Washington D.C., District of Columbia, United States

Gainesville, Florida, United States

Sarasota, Florida, United States

Lawrenceville, Georgia, United States

Chicago, Illinois, United States

Louisville, Kentucky, United States

Baltimore, Maryland, United States

Ann Arbor, Michigan, United States

Hattiesburg, Mississippi, United States

Hackensack, New Jersey, United States

Morristown, New Jersey, United States

New York, New York, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Arlington, Texas, United States

Lubbock, Texas, United States

Richmond, Virginia, United States

Seattle, Washington, United States

Milwaukee, Wisconsin, United States

Countries

United States

References

Paul A. Hamlin, Manish R. Patel, Don Stevens, Brian T. Hess, Javier Munoz, Tatyana A. Feldman, Sonali M. Smith, Greg P. Coffey, Muhtarjan Osman, Jaymes S Holland, Cristina B Guzman, Stephen D. Smith; Phase 2a Study of the Dual SYK/JAK Inhibitor Cerdulatinib (ALXN2075) As Monotherapy or in Combination with Rituximab in Patients with Relapsed/Refractory Follicular Lymphoma. Blood 2021; 138 (Supplement 1): 2423. doi: https://doi.org/10.1182/blood-2021-148313

Reference Type: RESULT

Coffey GP, Feng J, Betz A, Pandey A, Birrell M, Leeds JM, Der K, Kadri S, Lu P, Segal J, Wang YL, Michelson G, Curnutte JT, Conley PB. Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B-cell Malignancies. Clin Cancer Res. 2019 Feb 15;25(4):1174-1184. doi: 10.1158/1078-0432.CCR-18-1047. Epub 2018 Oct 17.

Reference Type: DERIVED

PMID: 30333224 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

13-601

Identifier Type: -

Identifier Source: org_study_id