Follicular Lymphoma (FL/Indolent NHL)Phase 1/2NCT01994382

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

A Phase 1/2 study testing Cerdulatinib and Rituximab in people with Follicular Lymphoma (FL/Indolent NHL) and Aggressive NHL (a NHL), run by Alexion Pharmaceuticals, Inc. at 23 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Follicular Lymphoma (FL/Indolent NHL), Aggressive NHL (a NHL), Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
What is being tested?: Cerdulatinib and Rituximab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 260 participants
Where: 23 sitesUnited States
Study dates: 30 Aug 2013to 15 Dec 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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≥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

Who cannot join

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).

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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 locations and contacts

23 sites in 1 country.

City, postcode or hospital

23 sites in 1 country

United States23 sites

Study site
Ann Arbor, Michigan, 48109
Study site
Arlington, Texas, 76012
Study site
Baltimore, Maryland, 21229
Study site
Charleston, South Carolina, 29412
Study site
Chicago, Illinois, 60637
Study site
Gainesville, Florida, 32608
Study site
Gilbert, Arizona, 85234
Study site
Hackensack, New Jersey, 07601
Study site
Hattiesburg, Mississippi, 39402
Study site
Huntsville, Alabama, 35805
Study site
Lawrenceville, Georgia, 30046
Study site
Los Angeles, California, 90095
Study site
Louisville, Kentucky, 40207
Study site
Lubbock, Texas, 79410
Study site
Milwaukee, Wisconsin, 53226
Study site
Morristown, New Jersey, 07960
Study site
New York, New York, 10021
Study site
Palo Alto, California, 94304
Study site
Philadelphia, Pennsylvania, 19104
Study site
Richmond, Virginia, 23226
Study site
Sarasota, Florida, 34232
Study site
Seattle, Washington, 98109
Study site
Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase 1/2a Open-Label, Multi-Dose, Multi-Center Escalation and Exploratory Study of Cerdulatinib (PRT062070) in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) or B-Cell or T-Cell Non-Hodgkin Lymphoma (NHL)

Read the 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)
Being tested: Cerdulatinib, Rituximab
Keywords: Leukemia, Lymphocytic, Chronic, B Cell
Medical subject headings: Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, T-Cell, Lymphoma, T-Cell, Cutaneous, Lymphoma, B-Cell, Leukemia, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CerdulatinibDrug
Also called PRT062070, ALXN2075
Oral capsule
RituximabBiological
Also called Rituxan®, Truxima®, Rixathon®, Ruxience®
IV infusion

Study groups in NCT01994382
Study group	Role	What they receive
Phase 1 Cerdulatinib	Experimental	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. Receives: Drug: Cerdulatinib
Phase 2a Cerdulatinib	Experimental	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. Receives: Drug: Cerdulatinib
Phase 2a Cerdulatinib plus Rituximab	Experimental	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. Receives: Drug: Cerdulatinib; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT)
DLT was defined as any of the following toxicities, possibly or probably related to cerdulatinib, and clinically significant (in the judgement of Investigator): -Febrile neutropenia (absolute neutrophil count <1000/microliter [μL] and temperature ≥38.5°Celcius). -Grade 4 neutropenia for >5 days. -Grade 4 thrombocytopenia with or without bleeding. -Grade 3 thrombocytopenia with bleeding. -Grade 4 anemia, unexplained by underlying disease. -Grade 3 or greater nausea, vomiting, or diarrhea if persistent despite optimal antiemetic or anti-diarrheal therapy. -Grade 3 or greater increase in transaminases lasting >5 days. -Grade 3 or greater fatigue persisting >7 days in absence of any other underlying cause. -Any other Grade 3 or greater non-hematologic toxicity (except fatigue as noted above) considered clinically significant by Investigator. -Toxicity of any grade resulting in dose delay of >7 days. -Toxicity resulting in study drug discontinuation prior to completion of Cycle 1.
Measured: Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days)
Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
CR included: -Via a positron emission tomography (PET)/computed tomography (CT) scan, score of 1 (no uptake above background), 2 (uptake of <mediastinum), or 3 (uptake of >mediastinum but <liver) for lymph nodes and extralymphatic sites; no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. -Via CT scan, target nodes/nodal masses regressed to <1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; organ enlargement has regressed to normal; and bone marrow was normal by morphology and if indeterminate, immunohistochemistry was negative.
PR included: -Via a PET/CT scan, score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual masses of any size. -Via CT scan, >50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

Secondary outcomes (7)

Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
CR included: -Via a PET/CT scan, score of 1 (no uptake above background), 2 (uptake of <mediastinum), or 3 (uptake of >mediastinum but <liver) for lymph nodes and extralymphatic sites; no new lesions; and no evidence of FDG-avid disease in bone marrow. -Via CT scan, target nodes/nodal masses regressed to <1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement has regressed to normal; and bone marrow was normal by morphology and if indeterminate, immunohistochemistry was negative.
PR included: -Via a PET/CT scan, a score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual masses of any size. -Via CT scan, >50% decrease in the sum of the product of perpendicular diameters for multiple lesion of up to 6 target measurable nodes and extranodal sites.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Phase 1: Number of Participants Achieving Clinical Benefit
Clinical benefit was defined as achieving stable disease (SD) or better, as assessed by the Investigator. SD included: -Via a PET/CT scan, a score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with no significant change in FDG uptake from baseline at interim or end of treatment; no new lesions; and no change from baseline in bone marrow. -Via CT scan, <50% decrease from baseline in sum of products of the greatest perpendicular diameters (SPD) of up to 6 dominant, measurable nodes and extranodal sites; no increase consistent with progression in nonmeasured lesions or organ enlargement; and no new lesions.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE)
An AE is any untoward medical occurrence, which may or may not have a causal relationship to the study drug, including: unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug; any newly occurring event or exacerbation of previous condition (for example, increase in severity or frequency) since the administration of study drug; recurrence of an intermittent medical condition not present at baseline; any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug; and AEs related to a study intervention. An SAE is an AE that is fatal, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Measured: Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days])
Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib
Measured: Cycle (C)1 Day (D)1: predose (0), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, and 72 hours postdose (except 15mg QD); C1D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (15mg QD); C2D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (all doses)
Phase 2a: Median Time to Progression-Free Survival (PFS)
PFS=(first documentation of disease progression [DP] or death [whichever occurred first]-study drug first dose date+1)/30.4375 in months. PFS right censored for 1 of these conditions: 1) no baseline disease assessments; 2) starting new anticancer therapy before documented DP/death; 3) DP/death immediately after >6 months since last disease assessment (or >12 months if after last cycle); \& alive without documented DP. 95% confidence interval estimated using Brookmeyer method. DP included: -Via a PET/CT scan, score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with uptake increase in intensity, new FDG-avid foci, \& no nonmeasured lesions. -Via CT, abnormal individual node/lesion with significant LDi or shortest axis perpendicular to LDi increase; prior splenomegaly, >50% splenic length increase; if no prior splenomegaly, ≥2 cm splenic length increase; new or recurrent splenomegaly; new/clear progression of preexisting nonmeasured lesions.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Phase 2a: Number of Participants Achieving Clinical Benefit
Clinical benefit was defined as achieving SD or better, as assessed by the Investigator. SD included: -Via a PET/CT scan, a score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with no significant change in FDG uptake from baseline at interim or end of treatment; no new lesions; and no change from baseline in bone marrow. -Via CT scan, <50% decrease from baseline in sum of products of the greatest perpendicular diameters (SPD) of up to 6 dominant, measurable nodes and extranodal sites; no increase consistent with progression in nonmeasured lesions or organ enlargement; and no new lesions.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR)
DMR was defined as achieving a ≥50% decrease from baseline in the SPD of the target nodal and extranodal lesions. SPD at a visit was considered missing if any target lesion was not evaluated.
Measured: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Aug 201315 Dec 2020

First posted25 Nov 2013 (estimated)
Study start30 Aug 2013
Primary completion15 Dec 2020
Study completion15 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Follicular Lymphoma (FL/Indolent NHL)Studies of the same condition, open and under way.
More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 260 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01994382
Sponsor's protocol ID: 13-601
Status last verified: Apr 2022
First submitted: 8 Nov 2013
Last updated: 5 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Expanded access: Available

Publications

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
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.
PubMed 30333224

Study at a glance

From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2a Open-Label, Multi-Dose, Multi-Center Escalation and Exploratory Study of Cerdulatinib (PRT062070) in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) or B-Cell or T-Cell Non-Hodgkin Lymphoma (NHL)
ClinicalTrials.gov ID: NCT01994382
Acronym / sponsor ID: 13-601
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)
Keywords: Leukemia, Lymphocytic, Chronic, B Cell
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 260 participants (actual)
Lead sponsor: Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Collaborators: Portola Pharmaceuticals
Study start: 30 Aug 2013 (actual)
Primary completion: 15 Dec 2020 (actual)
Study completion: 15 Dec 2020 (actual)
First posted: 25 Nov 2013 (estimated)
Results: Posted 5 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Phase 1 Cerdulatinib	Experimental	Drug: CerdulatinibDuring 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.
Phase 2a Cerdulatinib	Experimental	Drug: CerdulatinibDuring 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.
Phase 2a Cerdulatinib plus Rituximab	Experimental	Drug: Cerdulatinib, Biological: RituximabDuring 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

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

Key exclusion criteria (15 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CerdulatinibAlso: PRT062070, ALXN2075Oral capsule	Drug	Phase 1 Cerdulatinib, Phase 2a Cerdulatinib, Phase 2a Cerdulatinib plus Rituximab
RituximabAlso: Rituxan®, Truxima®, Rixathon®, Ruxience®IV infusion	Biological	Phase 2a Cerdulatinib plus Rituximab

Primary outcome

Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT)
Time frame: Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days)
DLT was defined as any of the following toxicities, possibly or probably related to cerdulatinib, and clinically significant (in the judgement of Investigator): -Febrile neutropenia (absolute neutrophil count <1000/microliter [μL] and temperature ≥38.5°Celcius). -Grade 4 neutropenia for >5 days. -Grade 4 thrombocytopenia with or without bleeding. -Grade 3 thrombocytopenia with bleeding. -Grade 4 anemia, unexplained by underlying disease. -Grade 3 or greater nausea, vomiting, or diarrhea if persistent despite optimal antiemetic or anti-diarrheal therapy. -Grade 3 or greater increase in transaminases lasting >5 days. -Grade 3 or greater fatigue persisting >7 days in absence of any other underlying cause. -Any other Grade 3 or greater non-hematologic toxicity (except fatigue as noted above) considered clinically significant by Investigator. -Toxicity of any grade resulting in dose delay of >7 days. -Toxicity resulting in study drug discontinuation prior to completion of Cycle 1.
Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
CR included: -Via a positron emission tomography (PET)/computed tomography (CT) scan, score of 1 (no uptake above background), 2 (uptake of <mediastinum), or 3 (uptake of >mediastinum but <liver) for lymph nodes and extralymphatic sites; no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. -Via CT scan, target nodes/nodal masses regressed to <1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; organ enlargement has regressed to normal; and bone marrow was normal by morphology and if indeterminate, immunohistochemistry was negative. PR included: -Via a PET/CT scan, score of 4 (uptake of moderately >liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual masses of any size. -Via CT scan, >50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites.

7 secondary outcomes

Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Phase 1: Number of Participants Achieving Clinical Benefit
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE)
Time frame: Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days])
Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib
Time frame: Cycle (C)1 Day (D)1: predose (0), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, and 72 hours postdose (except 15mg QD); C1D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (15mg QD); C2D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (all doses)
Phase 2a: Median Time to Progression-Free Survival (PFS)
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Phase 2a: Number of Participants Achieving Clinical Benefit
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR)
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

Results and safety

Results posted to the registry on 5 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1: Cerdulatinib 15 Milligrams (mg) Once Daily (QD)	3	0
Phase 1: Cerdulatinib 30 mg QD	6	0
Phase 1: Cerdulatinib 45 mg QD	7	0
Phase 1: Cerdulatinib 15 mg Twice Daily (BID)	3	0
Phase 1: Cerdulatinib 40 mg QD	3	0
Phase 1: Cerdulatinib 20 mg BID	3	0
Phase 1: Cerdulatinib 50 mg QD	4	0
Phase 1: Cerdulatinib 65 mg QD	6	0
Phase 1: Cerdulatinib 100 mg QD	3	0
Phase 1: Cerdulatinib 45 mg BID	5	0
Phase 2a: Cerdulatinib (FL Cohort)	42	0
Phase 2a: Cerdulatinib (MZL/WM Cohort)	12	0
Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort)	26	0
Phase 2a: Cerdulatinib (aNHL Cohort)	6	0
Phase 2a: Cerdulatinib (CLL/SLL Cohort)	28	0
Phase 2a: Cerdulatinib (PTCL Cohort)	65	0
Phase 2a: Cerdulatinib (CTCL Cohort)	41	0

Primary outcome: Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT)

Time frame: Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days). Count of participants. Unit: Participants

Measure	Phase 1: Cerdulatinib 15 mg QD n = 3	Phase 1: Cerdulatinib 30 mg QD n = 6	Phase 1: Cerdulatinib 45 mg QD n = 7	Phase 1: Cerdulatinib 15 mg BID n = 3	Phase 1: Cerdulatinib 40 mg QD n = 3	Phase 1: Cerdulatinib 20 mg BID n = 3	Phase 1: Cerdulatinib 50 mg QD n = 4	Phase 1: Cerdulatinib 65 mg QD n = 6	Phase 1: Cerdulatinib 100 mg QD n = 3	Phase 1: Cerdulatinib 45 mg BID n = 5
Value	0	0	0	0	0	0	0	0	1	2

Population analysed: The Safety Analysis Population included participants who received at least 1 dose of study drug. Only data from participants in Phase 1 cohorts (arms) were applicable and evaluated for this Outcome Measure. Evaluable participants for this Outcome Measure must have received 80% of doses in Cycle 1 or withdrawn from study drug due to drug-related toxicity.

Primary outcome: Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator

Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days]). Count of participants. Unit: Participants

Measure	Phase 2a: Cerdulatinib (FL Cohort) With ≤3 Prior Regimen n = 24	Phase 2a: Cerdulatinib (FL Cohort) With ≥4 Prior Regimen n = 10	Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≤3 Prior Regimen n = 16	Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≥4 Prior Regimen n = 10	Phase 2a: Cerdulatinib (PTCL Cohort) With AITL/TFH n = 27	Phase 2a: Cerdulatinib (PTCL Cohort) With NOS n = 9	Phase 2a: Cerdulatinib (PTCL Cohort) With Other n = 22
Value	12	6	15	5	14	0	7

Population analysed: The Efficacy Analysis Population included all participants who took at least 1 dose of study drug and had at least 1 post-baseline Investigator response assessment. Only the cohorts (arms) with participants with FL or with PTCL were applicable and evaluated for this Outcome Measure. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days]). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1: Cerdulatinib 15 mg QD	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1: Cerdulatinib 30 mg QD	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
Phase 1: Cerdulatinib 45 mg QD	4 of 7 (57.1%)	7 of 7 (100%)	0 of 7
Phase 1: Cerdulatinib 15 mg BID	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1: Cerdulatinib 40 mg QD	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
Phase 1: Cerdulatinib 20 mg BID	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1: Cerdulatinib 50 mg QD	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Phase 1: Cerdulatinib 65 mg QD	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
Phase 1: Cerdulatinib 100 mg QD	2 of 3 (66.7%)	3 of 3 (100%)	1 of 3
Phase 1: Cerdulatinib 45 mg BID	3 of 5 (60%)	5 of 5 (100%)	1 of 5
Phase 2a: Cerdulatinib (FL Cohort)	22 of 42 (52.4%)	42 of 42 (100%)	0 of 42
Phase 2a: Cerdulatinib (MZL/WM Cohort)	2 of 12 (16.7%)	12 of 12 (100%)	0 of 12
Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort)	7 of 26 (26.9%)	26 of 26 (100%)	0 of 26
Phase 2a: Cerdulatinib (aNHL Cohort)	3 of 6 (50%)	6 of 6 (100%)	0 of 6
Phase 2a: Cerdulatinib (CLL/SLL Cohort)	17 of 28 (60.7%)	28 of 28 (100%)	0 of 28
Phase 2a: Cerdulatinib (PTCL Cohort)	42 of 65 (64.6%)	65 of 65 (100%)	1 of 65
Phase 2a: Cerdulatinib (CTCL Cohort)	21 of 41 (51.2%)	41 of 41 (100%)	0 of 41

Limitations and caveats (from the sponsor): Key limitations of the study included that it was originally a single-arm, short-term study; disease progression was included as an AE; inadequate follow-up for death or progression; a lack of use of antimicrobial prophylaxis; and no uniform gastrointestinal toxicity management algorithm. These limitations impacted dose reduction and discontinuations due to treatment emergent AEs. In addition, monitoring issues due to the COVID-19 pandemic also factored into data collection and verification.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationPaul 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
Derived from this study: PubMed 30333224Coffey 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Portola Study Director study director

Portola Pharmaceuticals

23 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) (time frame: Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01994382, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2022; AzTrials last refreshed its copy on 26 Oct 2026.