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

Sponsor
Alexion Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01994382
Collaborator
Portola Pharmaceuticals (Industry)
260
Enrollment
23
Locations
3
Arms
87.5
Actual Duration (Months)
11.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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

Study Type:
Interventional
Actual Enrollment :
260 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Aug 30, 2013
Actual Primary Completion Date :
Dec 15, 2020
Actual Study Completion Date :
Dec 15, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Cerdulatinib
Oral capsule
Other Names:
  • PRT062070
  • ALXN2075

    		•
    Experimental: 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.

    Drug: Cerdulatinib
    Oral capsule
    Other Names:
  • PRT062070
  • ALXN2075

    		•
    Experimental: 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.

    Drug: Cerdulatinib
    Oral capsule
    Other Names:
  • PRT062070
  • ALXN2075

    • Biological: Rituximab
    IV infusion
    Other Names:
  • Rituxan®
  • Truxima®
  • Rixathon®
  • Ruxience®
  • MabThera®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) [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.

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

    Secondary Outcome Measures

    1. Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator [Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])]

      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.

    2. Phase 1: Number of Participants Achieving Clinical Benefit [Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])]

      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.

    3. Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) [Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days])]

      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.

    4. Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib [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)]

    5. Phase 2a: Median Time to Progression-Free Survival (PFS) [Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])]

      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.

    6. Phase 2a: Number of Participants Achieving Clinical Benefit [Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])]

      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.

    7. Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) [Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Huntsville Alabama United States 35805
    2 Gilbert Arizona United States 85234
    3 Los Angeles California United States 90095
    4 Palo Alto California United States 94304
    5 Washington District of Columbia United States 20007
    6 Gainesville Florida United States 32608
    7 Sarasota Florida United States 34232
    8 Lawrenceville Georgia United States 30046
    9 Chicago Illinois United States 60637
    10 Louisville Kentucky United States 40207
    11 Baltimore Maryland United States 21229
    12 Ann Arbor Michigan United States 48109
    13 Hattiesburg Mississippi United States 39402
    14 Hackensack New Jersey United States 07601
    15 Morristown New Jersey United States 07960
    16 New York New York United States 10021
    17 Philadelphia Pennsylvania United States 19104
    18 Charleston South Carolina United States 29412
    19 Arlington Texas United States 76012
    20 Lubbock Texas United States 79410
    21 Richmond Virginia United States 23226
    22 Seattle Washington United States 98109
    23 Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Alexion Pharmaceuticals
    • Portola Pharmaceuticals

    Investigators

    • Study Director: Portola Study Director, Portola Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Alexion Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01994382
    Other Study ID Numbers:
    • 13-601
    First Posted:
    Nov 25, 2013
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Keywords provided by Alexion Pharmaceuticals
    Leukemia
    Lymphocytic
    Chronic
    B Cell
    Additional relevant MeSH terms:
    Lymphoma
    Leukemia
    Lymphoma, Non-Hodgkin
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Lymphoma, B-Cell
    Rituximab

    Study Results

    Participant Flow

    Recruitment Details This was an open-label study with 2 phases.
    Pre-assignment Detail Phase 1: dose-escalation portion of study, participants received doses of cerdulatinib at assigned regimen. Phase 2a: participants were enrolled into cohorts based on cancer type and received single agent cerdulatinib except for 1 cohort, participants received cerdulatinib+rituximab. Three participants in Phase 1 rolled over to Phase 2; their data are included in respective arms in both phases. Therefore, the data are included twice in the Totals for Participant Flow & Baseline Characteristics.
    Arm/Group Title Phase 1: Cerdulatinib 15 Milligrams (mg) Once Daily (QD) Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg Twice Daily (BID) Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants with follicular lymphoma (FL) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with marginal zone lymphoma/Waldenström's macroglobulinemia (MZL/WM) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received intravenous (IV) injections of rituximab 375 milligrams (mg)/square meter (m^2) on Days 1, 8, 15, and 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, and 10. Participants with aggressive non-Hodgkin lymphoma (aNHL) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with chronic lymphocytic leukemia/small cell lymphocytic lymphoma (CLL/SLL) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with peripheral T-cell lymphoma (PTCL) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with cutaneous T-cell lymphoma (CTCL) received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable.
    Period Title: Overall Study
    STARTED 3 6 7 3 3 3 4 6 3 5 42 12 26 6 28 65 41
    Received at Least 1 Dose of Study Drug 3 6 7 3 3 3 4 6 3 5 42 12 26 6 28 65 41
    COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 3 6 7 3 3 3 4 6 3 5 42 12 26 6 28 65 41

    Baseline Characteristics

    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort) Total
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with MZL/WM received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID. Participants also received IV injections 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. Participants with aNHL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with CLL/SLL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with CTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Total of all reporting groups
    Overall Participants 3 6 7 3 3 3 4 6 3 5 42 12 26 6 28 65 41 263
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    33.3%
    1
    16.7%
    3
    42.9%
    0
    0%
    3
    100%
    2
    66.7%
    0
    0%
    1
    16.7%
    1
    33.3%
    1
    20%
    23
    54.8%
    7
    58.3%
    13
    50%
    2
    33.3%
    8
    28.6%
    33
    50.8%
    21
    51.2%
    120
    45.6%
    >=65 years
    2
    66.7%
    5
    83.3%
    4
    57.1%
    3
    100%
    0
    0%
    1
    33.3%
    4
    100%
    5
    83.3%
    2
    66.7%
    4
    80%
    19
    45.2%
    5
    41.7%
    13
    50%
    4
    66.7%
    20
    71.4%
    32
    49.2%
    20
    48.8%
    143
    54.4%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    2
    33.3%
    3
    42.9%
    2
    66.7%
    0
    0%
    2
    66.7%
    1
    25%
    1
    16.7%
    0
    0%
    2
    40%
    16
    38.1%
    4
    33.3%
    9
    34.6%
    1
    16.7%
    12
    42.9%
    24
    36.9%
    18
    43.9%
    97
    36.9%
    Male
    3
    100%
    4
    66.7%
    4
    57.1%
    1
    33.3%
    3
    100%
    1
    33.3%
    3
    75%
    5
    83.3%
    3
    100%
    3
    60%
    26
    61.9%
    8
    66.7%
    17
    65.4%
    5
    83.3%
    16
    57.1%
    41
    63.1%
    23
    56.1%
    166
    63.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    2
    4.8%
    1
    8.3%
    1
    3.8%
    0
    0%
    1
    3.6%
    6
    9.2%
    1
    2.4%
    13
    4.9%
    Not Hispanic or Latino
    3
    100%
    6
    100%
    7
    100%
    3
    100%
    3
    100%
    2
    66.7%
    4
    100%
    6
    100%
    3
    100%
    3
    60%
    37
    88.1%
    10
    83.3%
    24
    92.3%
    5
    83.3%
    26
    92.9%
    53
    81.5%
    37
    90.2%
    232
    88.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    3
    7.1%
    1
    8.3%
    1
    3.8%
    1
    16.7%
    1
    3.6%
    6
    9.2%
    3
    7.3%
    18
    6.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    1
    2.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    3
    1.1%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    4.8%
    0
    0%
    1
    3.8%
    0
    0%
    1
    3.6%
    2
    3.1%
    0
    0%
    6
    2.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    1
    0.4%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    1
    8.3%
    2
    7.7%
    0
    0%
    3
    10.7%
    10
    15.4%
    11
    26.8%
    29
    11%
    White
    3
    100%
    6
    100%
    7
    100%
    3
    100%
    2
    66.7%
    3
    100%
    4
    100%
    6
    100%
    3
    100%
    4
    80%
    36
    85.7%
    11
    91.7%
    22
    84.6%
    6
    100%
    23
    82.1%
    48
    73.8%
    24
    58.5%
    211
    80.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    4.8%
    0
    0%
    1
    3.8%
    0
    0%
    1
    3.6%
    5
    7.7%
    4
    9.8%
    13
    4.9%

    Outcome Measures

    1. Primary Outcome
    Title Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT)
    Description 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.
    Time Frame Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles.
    Measure Participants 3 6 7 3 3 3 4 6 3 5
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    2
    40%
    2. Primary Outcome
    Title Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 2a: Cerdulatinib (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib (PTCL Cohort) With AITL/TFH Phase 2a: Cerdulatinib (PTCL Cohort) With NOS Phase 2a: Cerdulatinib (PTCL Cohort) With Other
    Arm/Group Description Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL angioimmunoblastic T-cell lymphoma (AITCL/AITL) and PTCL with T-follicular helper phenotype (TFH). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL not otherwise specified (NOS). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of other PTCL pathology subgroups not included in AITL/TFH or NOS subgroups.
    Measure Participants 24 10 16 10 27 9 22
    Count of Participants [Participants]
    12
    400%
    6
    100%
    15
    214.3%
    5
    166.7%
    14
    466.7%
    0
    0%
    7
    175%
    3. Secondary Outcome
    Title Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles.
    Measure Participants 3 6 7 3 3 3 4 6 3 5
    Count of Participants [Participants]
    0
    0%
    1
    16.7%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    2
    40%
    4. Secondary Outcome
    Title Phase 1: Number of Participants Achieving Clinical Benefit
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles.
    Measure Participants 3 6 7 3 3 3 4 6 3 5
    Count of Participants [Participants]
    2
    66.7%
    4
    66.7%
    4
    57.1%
    1
    33.3%
    1
    33.3%
    0
    0%
    2
    50%
    2
    33.3%
    1
    33.3%
    1
    20%
    5. Secondary Outcome
    Title Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE)
    Description 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.
    Time Frame Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days])

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Population included participants who received at least 1 dose of study drug.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants with MZL/WM received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants also received IV injections 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. Participants with aNHL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants with CLL/SLL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval. Participants with CTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable, at the discretion of the Investigator based upon clinical judgment and with Sponsor Medical Monitor approval.
    Measure Participants 3 6 7 3 3 3 4 6 3 5 42 12 26 6 28 65 41
    AE
    3
    100%
    6
    100%
    7
    100%
    3
    100%
    3
    100%
    3
    100%
    4
    100%
    6
    100%
    3
    100%
    5
    100%
    42
    100%
    12
    100%
    26
    100%
    6
    100%
    28
    100%
    65
    100%
    41
    100%
    SAE
    0
    0%
    2
    33.3%
    4
    57.1%
    0
    0%
    1
    33.3%
    0
    0%
    2
    50%
    2
    33.3%
    2
    66.7%
    3
    60%
    22
    52.4%
    2
    16.7%
    7
    26.9%
    3
    50%
    17
    60.7%
    42
    64.6%
    21
    51.2%
    6. Secondary Outcome
    Title Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic Analysis Population consisted of all participants who received the requisite treatments and have data at the required timepoints. Only data from participants in Phase 1 cohorts (arms) were applicable and evaluated for this Outcome Measure. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified timepoints.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles.
    Measure Participants 3 6 7 3 3 3 4 5 3 5
    Day 1 of Cycle 1
    709.6
    (37.823)
    1040
    (347.34)
    1826
    (713.67)
    601.4
    (118.04)
    2064
    (666.52)
    674.5
    (113.34)
    2465
    (305.70)
    2719
    (1208.2)
    2758
    (969.37)
    1335
    (530.56)
    Day 1 of Cycle 2
    1321
    (140.21)
    1900
    (918.79)
    6804
    (3065.6)
    2129
    (533.14)
    6313
    (166.81)
    2779
    (458.94)
    5871
    (3685.1)
    6215
    (249.64)
    7. Secondary Outcome
    Title Phase 2a: Median Time to Progression-Free Survival (PFS)
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 2a: Cerdulatinib (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib (PTCL Cohort) With AITL/TFH Phase 2a: Cerdulatinib (PTCL Cohort) With NOS Phase 2a: Cerdulatinib (PTCL Cohort) With Other
    Arm/Group Description Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL angioimmunoblastic T-cell lymphoma (AITCL/AITL) and PTCL with T-follicular helper phenotype (TFH). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL not otherwise specified (NOS). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of other PTCL pathology subgroups not included in AITL/TFH or NOS subgroups.
    Measure Participants 24 10 16 10 27 9 22
    Median (95% Confidence Interval) [months]
    12.68
    3.61
    18.33
    NA
    4.57
    1.18
    3.45
    8. Secondary Outcome
    Title Phase 2a: Number of Participants Achieving Clinical Benefit
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 2a: Cerdulatinib (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib (PTCL Cohort) With AITL/TFH Phase 2a: Cerdulatinib (PTCL Cohort) With NOS Phase 2a: Cerdulatinib (PTCL Cohort) With Other
    Arm/Group Description Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL angioimmunoblastic T-cell lymphoma (AITCL/AITL) and PTCL with T-follicular helper phenotype (TFH). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL not otherwise specified (NOS). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of other PTCL pathology subgroups not included in AITL/TFH or NOS subgroups.
    Measure Participants 24 10 16 10 27 9 22
    Count of Participants [Participants]
    19
    633.3%
    8
    133.3%
    16
    228.6%
    10
    333.3%
    17
    566.7%
    2
    66.7%
    16
    400%
    9. Secondary Outcome
    Title Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR)
    Description 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.
    Time Frame Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Phase 2a: Cerdulatinib (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≤3 Prior Regimen Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) With ≥4 Prior Regimen Phase 2a: Cerdulatinib (PTCL Cohort) With AITL/TFH Phase 2a: Cerdulatinib (PTCL Cohort) With NOS Phase 2a: Cerdulatinib (PTCL Cohort) With Other
    Arm/Group Description Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≤3 times before study start. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants in this cohort received prior treatment regimen of ≥4 times before study start. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL angioimmunoblastic T-cell lymphoma (AITCL/AITL) and PTCL with T-follicular helper phenotype (TFH). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of PTCL not otherwise specified (NOS). Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. This cohort included participants with cancer type of other PTCL pathology subgroups not included in AITL/TFH or NOS subgroups.
    Measure Participants 24 10 16 10 27 9 22
    Count of Participants [Participants]
    14
    466.7%
    5
    83.3%
    14
    200%
    7
    233.3%
    15
    500%
    1
    33.3%
    5
    125%

    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])
    Adverse Event Reporting Description The Safety Analysis Population included participants who received at least 1 dose of study drug.
    Arm/Group Title Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Arm/Group Description Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 30 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 15 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 40 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 20 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 50 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 65 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 100 mg on Day 1 and then QD starting on Day 4 in 28-day cycles for up to 10 cycles. Participants received oral cerdulatinib at 45 mg on Day 1 and then BID starting on Day 4 in 28-day cycles for up to 10 cycles. Participants with FL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with MZL/WM received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with FL received oral cerdulatinib at starting doses of 30 or 20 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants also received IV injections 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. Participants with aNHL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with CLL/SLL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with PTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable. Participants with CTCL received oral cerdulatinib at starting doses of 35 or 30 mg BID on Day 1 in 28-day cycles for up to 10 cycles. Doses of cerdulatinib could have been reduced to a minimum dose of 15 mg BID or increased to a maximum dose of 30 mg BID, when applicable.
    All Cause Mortality
    Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Serious Adverse Events
    Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 2/6 (33.3%) 4/7 (57.1%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/4 (50%) 2/6 (33.3%) 2/3 (66.7%) 3/5 (60%) 22/42 (52.4%) 2/12 (16.7%) 7/26 (26.9%) 3/6 (50%) 17/28 (60.7%) 42/65 (64.6%) 21/41 (51.2%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Autoimmune haemolytic anaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Febrile neutropenia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 1/42 (2.4%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 1/28 (3.6%) 2/65 (3.1%) 0/41 (0%)
    Pancytopenia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 1/12 (8.3%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Methaemoglobinaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 1/65 (1.5%) 0/41 (0%)
    Haemolysis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Lymph node pain 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Neutropenia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Atrial fibrillation 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 1/41 (2.4%)
    Acute coronary syndrome 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Acute left ventricular failure 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Cardiac arrest 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Cardiomyopathy 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Tachycardia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Eye disorders
    Vision blurred 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Gastrointestinal disorders
    Diarrhoea 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 2/42 (4.8%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 2/28 (7.1%) 3/65 (4.6%) 2/41 (4.9%)
    Diverticulum 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Haematochezia 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Large intestine perforation 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Nausea 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Pancreatitis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 2/42 (4.8%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 1/65 (1.5%) 0/41 (0%)
    Abdominal pain 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 1/41 (2.4%)
    Vomiting 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Colitis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 1/65 (1.5%) 0/41 (0%)
    Lower gastrointestinal haemorrhage 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Dysphagia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Fistula of small intestine 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Small intestinal obstruction 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Uvulitis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Gastritis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Gastrointestinal haemorrhage 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    General disorders
    Disease progression 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Pyrexia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 1/12 (8.3%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 5/65 (7.7%) 0/41 (0%)
    Non-cardiac chest pain 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Death 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Mucosal inflammation 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Multiple organ dysfunction syndrome 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Sudden death 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Swelling face 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Systemic inflammatory response syndrome 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Immune system disorders
    Cytokine release syndrome 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Graft versus host disease 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Infections and infestations
    Pneumocystis jirovecii pneumonia 0/3 (0%) 1/6 (16.7%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Bronchitis 0/3 (0%) 1/6 (16.7%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Hepatic infection 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Lung infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Pneumonia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 5/26 (19.2%) 0/6 (0%) 4/28 (14.3%) 3/65 (4.6%) 2/41 (4.9%)
    Sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 2/28 (7.1%) 6/65 (9.2%) 2/41 (4.9%)
    Influenza 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 1/41 (2.4%)
    Nocardiosis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Bacteraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 2/28 (7.1%) 1/65 (1.5%) 0/41 (0%)
    Skin infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 1/41 (2.4%)
    Upper respiratory tract infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 1/65 (1.5%) 0/41 (0%)
    Cellulitis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Clostridium difficile infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Epstein-Barr virus infection reactivation 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Pneumonia bacterial 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 1/41 (2.4%)
    Septic shock 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Staphylococcal bacteraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 2/41 (4.9%)
    Urinary tract infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Brain abscess 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Bronchopulmonary aspergillosis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Corynebacterium sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Cytomegalovirus gastritis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Cytomegalovirus viraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Device related infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Escherichia bacteraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Gastroenteritis viral 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Herpes zoster 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Localised infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Neutropenic sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Pneumonia fungal 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/42 (0%) 0 0/12 (0%) 0 0/26 (0%) 0 0/6 (0%) 0 0/28 (0%) 0 0/65 (0%) 0 1/41 (2.4%) 0
    Pseudomonal sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Pyelonephritis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Scedosporium infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Soft tissue infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Staphylococcal infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Staphylococcal sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Streptococcal sepsis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    West Nile viral infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Wound infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Lumbar vertebral fracture 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/42 (0%) 0 0/12 (0%) 0 0/26 (0%) 0 0/6 (0%) 0 1/28 (3.6%) 0 0/65 (0%) 0 0/41 (0%) 0
    Toxicity to various agents 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Wrist fracture 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Investigations
    Platelet count decreased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Amylase increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Lymphocyte count increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Neutrophil count decreased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 3/41 (7.3%)
    Hyponatraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 2/28 (7.1%) 1/65 (1.5%) 0/41 (0%)
    Tumour lysis syndrome 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Decreased appetite 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Gout 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Hyperkalaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Hypoglycaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Hypercalcaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 1/12 (8.3%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 1/26 (3.8%) 1/6 (16.7%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Back pain 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic lymphocytic leukaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Non-Hodgkin lymphoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Neoplasm progression 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 13/65 (20%) 2/41 (4.9%)
    Diffuse large B-cell lymphoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 1/41 (2.4%)
    Adenocarcinoma metastatic 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Anal squamous cell carcinoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Oesophageal adenocarcinoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    T-cell lymphoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    B-cell lymphoma 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Nervous system disorders
    Syncope 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 2/65 (3.1%) 0/41 (0%)
    Acute motor axonal neuropathy 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Cerebral haemorrhage 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Cerebrovascular accident 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Dysarthria 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Transient ischaemic attack 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Psychiatric disorders
    Confusional state 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 1/12 (8.3%) 1/26 (3.8%) 0/6 (0%) 1/28 (3.6%) 2/65 (3.1%) 0/41 (0%)
    Haematuria 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 1/41 (2.4%)
    Pulmonary embolism 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Pneumonitis 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 2/42 (4.8%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Acute respiratory failure 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 2/28 (7.1%) 0/65 (0%) 0/41 (0%)
    Pneumonia aspiration 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 1/6 (16.7%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Respiratory failure 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 0/41 (0%)
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Rash 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 1/41 (2.4%)
    Vascular disorders
    Hypotension 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Embolism 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 2/28 (7.1%) 1/65 (1.5%) 0/41 (0%)
    Hypertension 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Orthostatic hypotension 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 1/65 (1.5%) 0/41 (0%)
    Other (Not Including Serious) Adverse Events
    Phase 1: Cerdulatinib 15 mg QD Phase 1: Cerdulatinib 30 mg QD Phase 1: Cerdulatinib 45 mg QD Phase 1: Cerdulatinib 15 mg BID Phase 1: Cerdulatinib 40 mg QD Phase 1: Cerdulatinib 20 mg BID Phase 1: Cerdulatinib 50 mg QD Phase 1: Cerdulatinib 65 mg QD Phase 1: Cerdulatinib 100 mg QD Phase 1: Cerdulatinib 45 mg BID Phase 2a: Cerdulatinib (FL Cohort) Phase 2a: Cerdulatinib (MZL/WM Cohort) Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) Phase 2a: Cerdulatinib (aNHL Cohort) Phase 2a: Cerdulatinib (CLL/SLL Cohort) Phase 2a: Cerdulatinib (PTCL Cohort) Phase 2a: Cerdulatinib (CTCL Cohort)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 6/6 (100%) 7/7 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 4/4 (100%) 6/6 (100%) 3/3 (100%) 5/5 (100%) 42/42 (100%) 12/12 (100%) 26/26 (100%) 6/6 (100%) 28/28 (100%) 65/65 (100%) 41/41 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 1/6 (16.7%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/4 (50%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 4/42 (9.5%) 4/12 (33.3%) 6/26 (23.1%) 2/6 (33.3%) 9/28 (32.1%) 21/65 (32.3%) 12/41 (29.3%)
    Neutropenia 0/3 (0%) 2/6 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 9/42 (21.4%) 2/12 (16.7%) 8/26 (30.8%) 0/6 (0%) 4/28 (14.3%) 13/65 (20%) 6/41 (14.6%)
    Thrombocytopenia 0/3 (0%) 0/6 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 1/12 (8.3%) 1/26 (3.8%) 0/6 (0%) 3/28 (10.7%) 2/65 (3.1%) 3/41 (7.3%)
    Gastrointestinal disorders
    Diarrhoea 0/3 (0%) 1/6 (16.7%) 3/7 (42.9%) 2/3 (66.7%) 2/3 (66.7%) 0/3 (0%) 2/4 (50%) 4/6 (66.7%) 3/3 (100%) 5/5 (100%) 23/42 (54.8%) 5/12 (41.7%) 21/26 (80.8%) 2/6 (33.3%) 20/28 (71.4%) 27/65 (41.5%) 20/41 (48.8%)
    Nausea 1/3 (33.3%) 1/6 (16.7%) 3/7 (42.9%) 0/3 (0%) 2/3 (66.7%) 2/3 (66.7%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%) 2/5 (40%) 23/42 (54.8%) 6/12 (50%) 13/26 (50%) 3/6 (50%) 14/28 (50%) 21/65 (32.3%) 17/41 (41.5%)
    Abdominal Pain 1/3 (33.3%) 0/6 (0%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 3/6 (50%) 2/3 (66.7%) 1/5 (20%) 13/42 (31%) 2/12 (16.7%) 7/26 (26.9%) 1/6 (16.7%) 6/28 (21.4%) 16/65 (24.6%) 3/41 (7.3%)
    Vomiting 2/3 (66.7%) 1/6 (16.7%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 10/42 (23.8%) 2/12 (16.7%) 8/26 (30.8%) 2/6 (33.3%) 2/28 (7.1%) 4/65 (6.2%) 6/41 (14.6%)
    Constipation 0/3 (0%) 1/6 (16.7%) 1/7 (14.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 9/42 (21.4%) 2/12 (16.7%) 6/26 (23.1%) 3/6 (50%) 6/28 (21.4%) 6/65 (9.2%) 5/41 (12.2%)
    Abdominal Distension 0/3 (0%) 1/6 (16.7%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 4/42 (9.5%) 0/12 (0%) 3/26 (11.5%) 1/6 (16.7%) 1/28 (3.6%) 4/65 (6.2%) 2/41 (4.9%)
    Gastrooesophageal Reflux Disease 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 8/42 (19%) 1/12 (8.3%) 5/26 (19.2%) 0/6 (0%) 1/28 (3.6%) 8/65 (12.3%) 3/41 (7.3%)
    Dyspepsia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 7/42 (16.7%) 2/12 (16.7%) 4/26 (15.4%) 1/6 (16.7%) 3/28 (10.7%) 2/65 (3.1%) 0/41 (0%)
    Flatulence 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 2/12 (16.7%) 2/26 (7.7%) 1/6 (16.7%) 3/28 (10.7%) 1/65 (1.5%) 3/41 (7.3%)
    General disorders
    Fatigue 0/3 (0%) 2/6 (33.3%) 6/7 (85.7%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 2/4 (50%) 5/6 (83.3%) 1/3 (33.3%) 3/5 (60%) 21/42 (50%) 7/12 (58.3%) 15/26 (57.7%) 2/6 (33.3%) 16/28 (57.1%) 18/65 (27.7%) 14/41 (34.1%)
    Pyrexia 0/3 (0%) 2/6 (33.3%) 4/7 (57.1%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 1/5 (20%) 12/42 (28.6%) 1/12 (8.3%) 5/26 (19.2%) 1/6 (16.7%) 6/28 (21.4%) 8/65 (12.3%) 4/41 (9.8%)
    Pain 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Oedema Peripheral 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 7/42 (16.7%) 0/12 (0%) 2/26 (7.7%) 0/6 (0%) 3/28 (10.7%) 4/65 (6.2%) 4/41 (9.8%)
    Chills 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 4/42 (9.5%) 3/12 (25%) 3/26 (11.5%) 0/6 (0%) 4/28 (14.3%) 1/65 (1.5%) 1/41 (2.4%)
    Asthenia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 6/42 (14.3%) 0/12 (0%) 1/26 (3.8%) 0/6 (0%) 2/28 (7.1%) 4/65 (6.2%) 2/41 (4.9%)
    Infections and infestations
    Upper Respiratory Tract Infection 0/3 (0%) 1/6 (16.7%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 0/5 (0%) 6/42 (14.3%) 0/12 (0%) 3/26 (11.5%) 0/6 (0%) 4/28 (14.3%) 7/65 (10.8%) 2/41 (4.9%)
    Urinary Tract Infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 5/42 (11.9%) 0/12 (0%) 4/26 (15.4%) 1/6 (16.7%) 4/28 (14.3%) 3/65 (4.6%) 5/41 (12.2%)
    Skin Infection 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 1/12 (8.3%) 0/26 (0%) 0/6 (0%) 1/28 (3.6%) 4/65 (6.2%) 5/41 (12.2%)
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 2/26 (7.7%) 1/6 (16.7%) 4/28 (14.3%) 2/65 (3.1%) 4/41 (9.8%)
    Investigations
    Weight Decreased 0/3 (0%) 1/6 (16.7%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 2/5 (40%) 2/42 (4.8%) 0/12 (0%) 5/26 (19.2%) 1/6 (16.7%) 9/28 (32.1%) 4/65 (6.2%) 1/41 (2.4%)
    Neutrophil Count Decreased 0/3 (0%) 0/6 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 5/42 (11.9%) 0/12 (0%) 2/26 (7.7%) 1/6 (16.7%) 3/28 (10.7%) 10/65 (15.4%) 1/41 (2.4%)
    Lipase Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 14/42 (33.3%) 3/12 (25%) 10/26 (38.5%) 0/6 (0%) 8/28 (28.6%) 19/65 (29.2%) 24/41 (58.5%)
    Amylase Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 13/42 (31%) 2/12 (16.7%) 7/26 (26.9%) 0/6 (0%) 6/28 (21.4%) 28/65 (43.1%) 21/41 (51.2%)
    Aspartate Aminotransferase Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 1/12 (8.3%) 4/26 (15.4%) 1/6 (16.7%) 1/28 (3.6%) 5/65 (7.7%) 7/41 (17.1%)
    Alanine Aminotransferase Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 2/26 (7.7%) 1/6 (16.7%) 0/28 (0%) 10/65 (15.4%) 5/41 (12.2%)
    Blood Creatinine Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 1/12 (8.3%) 2/26 (7.7%) 0/6 (0%) 1/28 (3.6%) 4/65 (6.2%) 4/41 (9.8%)
    Blood Lactate Dehydrogenase Increased 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 0/12 (0%) 3/26 (11.5%) 0/6 (0%) 1/28 (3.6%) 0/65 (0%) 7/41 (17.1%)
    Metabolism and nutrition disorders
    Decreased Appetite 1/3 (33.3%) 0/6 (0%) 3/7 (42.9%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 2/3 (66.7%) 1/5 (20%) 7/42 (16.7%) 1/12 (8.3%) 5/26 (19.2%) 2/6 (33.3%) 11/28 (39.3%) 8/65 (12.3%) 3/41 (7.3%)
    Dehydration 0/3 (0%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1/6 (16.7%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 1/12 (8.3%) 1/26 (3.8%) 1/6 (16.7%) 2/28 (7.1%) 4/65 (6.2%) 2/41 (4.9%)
    Hyperkalaemia 1/3 (33.3%) 0/6 (0%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Hyponatraemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 2/12 (16.7%) 2/26 (7.7%) 0/6 (0%) 4/28 (14.3%) 7/65 (10.8%) 2/41 (4.9%)
    Hypokalaemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 2/42 (4.8%) 1/12 (8.3%) 2/26 (7.7%) 1/6 (16.7%) 4/28 (14.3%) 5/65 (7.7%) 1/41 (2.4%)
    Hypophosphatemia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 2/42 (4.8%) 0/12 (0%) 2/26 (7.7%) 2/6 (33.3%) 4/28 (14.3%) 2/65 (3.1%) 2/41 (4.9%)
    Musculoskeletal and connective tissue disorders
    Back Pain 1/3 (33.3%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 7/42 (16.7%) 0/12 (0%) 3/26 (11.5%) 0/6 (0%) 2/28 (7.1%) 2/65 (3.1%) 3/41 (7.3%)
    Myalgia 0/3 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Arthralgia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 5/42 (11.9%) 1/12 (8.3%) 3/26 (11.5%) 0/6 (0%) 4/28 (14.3%) 3/65 (4.6%) 1/41 (2.4%)
    Pain In Extremity 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 4/42 (9.5%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 3/28 (10.7%) 3/65 (4.6%) 5/41 (12.2%)
    Nervous system disorders
    Headache 0/3 (0%) 0/6 (0%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%) 1/5 (20%) 11/42 (26.2%) 2/12 (16.7%) 4/26 (15.4%) 1/6 (16.7%) 7/28 (25%) 12/65 (18.5%) 3/41 (7.3%)
    Paraesthesia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 1/12 (8.3%) 0/26 (0%) 1/6 (16.7%) 1/28 (3.6%) 4/65 (6.2%) 1/41 (2.4%)
    Dysgeusia 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 5/42 (11.9%) 2/12 (16.7%) 4/26 (15.4%) 1/6 (16.7%) 7/28 (25%) 13/65 (20%) 8/41 (19.5%)
    Dizziness 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 8/42 (19%) 2/12 (16.7%) 5/26 (19.2%) 1/6 (16.7%) 8/28 (28.6%) 6/65 (9.2%) 3/41 (7.3%)
    Psychiatric disorders
    Insomnia 1/3 (33.3%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 1/5 (20%) 0/42 (0%) 0/12 (0%) 2/26 (7.7%) 0/6 (0%) 3/28 (10.7%) 4/65 (6.2%) 2/41 (4.9%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/3 (33.3%) 1/6 (16.7%) 3/7 (42.9%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%) 1/5 (20%) 7/42 (16.7%) 2/12 (16.7%) 4/26 (15.4%) 0/6 (0%) 9/28 (32.1%) 6/65 (9.2%) 6/41 (14.6%)
    Rhinorrhoea 1/3 (33.3%) 2/6 (33.3%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Dyspnoea 0/3 (0%) 0/6 (0%) 2/7 (28.6%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 9/42 (21.4%) 1/12 (8.3%) 4/26 (15.4%) 1/6 (16.7%) 5/28 (17.9%) 8/65 (12.3%) 1/41 (2.4%)
    Oropharyngeal Pain 0/3 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 2/5 (40%) 7/42 (16.7%) 0/12 (0%) 2/26 (7.7%) 1/6 (16.7%) 4/28 (14.3%) 7/65 (10.8%) 2/41 (4.9%)
    Sinus Congestion 1/3 (33.3%) 0/6 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 0/42 (0%) 0/12 (0%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 0/65 (0%) 0/41 (0%)
    Nasal Congestion 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 4/26 (15.4%) 0/6 (0%) 1/28 (3.6%) 1/65 (1.5%) 2/41 (4.9%)
    Skin and subcutaneous tissue disorders
    Night Sweats 1/3 (33.3%) 1/6 (16.7%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 5/42 (11.9%) 1/12 (8.3%) 0/26 (0%) 1/6 (16.7%) 2/28 (7.1%) 1/65 (1.5%) 1/41 (2.4%)
    Rash 0/3 (0%) 1/6 (16.7%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%) 1/5 (20%) 11/42 (26.2%) 0/12 (0%) 2/26 (7.7%) 0/6 (0%) 4/28 (14.3%) 8/65 (12.3%) 6/41 (14.6%)
    Rash Maculo-Papular 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 3/42 (7.1%) 0/12 (0%) 3/26 (11.5%) 1/6 (16.7%) 2/28 (7.1%) 3/65 (4.6%) 4/41 (9.8%)
    Pruritus 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 1/42 (2.4%) 2/12 (16.7%) 0/26 (0%) 0/6 (0%) 0/28 (0%) 5/65 (7.7%) 4/41 (9.8%)
    Vascular disorders
    Hypertension 0/3 (0%) 0/6 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%) 0/5 (0%) 10/42 (23.8%) 1/12 (8.3%) 8/26 (30.8%) 1/6 (16.7%) 4/28 (14.3%) 3/65 (4.6%) 3/41 (7.3%)

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Alexion Pharmaceuticals, Inc.
    Organization Alexion Pharmaceuticals, Inc.
    Phone +1.855.752.2356
    Email clinicaltrials@alexion.com
    Responsible Party:
    Alexion Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01994382
    Other Study ID Numbers:
    • 13-601
    First Posted:
    Nov 25, 2013
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022