Aggressive NHL (a NHL), B-cell Non Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma (FL/Indolent NHL), T-cell Lymphoma (PTCL and CTCL)
Conditions
Keywords
Leukemia, Lymphocytic, Chronic, B Cell
Brief summary
This study will identify the highest dose, and assess the safety, of cerdulatinib (PRT062070) that may be given in participants with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or non-hodgkin lymphoma.
Detailed description
This is an open-label, Phase 1/2a, multi-dose, multi-center trial of orally administered cerdulatinib assessing safety, tolerability, and pharmacokinetic (PK) parameters conducted in 2 phases: * Phase 1: Dose-escalation portion, during which participants will be enrolled to receive a single-agent cerdulatinib at their assigned dose level starting at 15 milligrams (mg) once daily (QD), administered in increasing doses until the maximum tolerated dose (MTD)/maximum administered dose (MAD) is identified. * Phase 2a: Consisting of planned cohorts based on cancer type. The participants will receive single agent cerdulatinib at a starting dose of 35, 30, or 20 mg twice daily (BID) for 28-day cycles except for one of the cohorts, the participants will receive cerdulatinib plus intravenous (IV) rituximab at 375 mg/square meter (m\^2) for 28-day cycles.
Interventions
Oral capsule
IV infusion
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
This was an open-label study with 2 phases.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Cerdulatinib 15 mg QD Participants received oral cerdulatinib at 15 mg QD starting on Day 1 in 21-day cycles for up to 10 cycles. | 3 |
| Phase 1: Cerdulatinib 30 mg QD 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. | 6 |
| Phase 1: Cerdulatinib 45 mg QD 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. | 7 |
| Phase 1: Cerdulatinib 15 mg BID 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. | 3 |
| Phase 1: Cerdulatinib 40 mg QD 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. | 3 |
| Phase 1: Cerdulatinib 20 mg BID 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. | 3 |
| Phase 1: Cerdulatinib 50 mg QD 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. | 4 |
| Phase 1: Cerdulatinib 65 mg QD 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. | 6 |
| Phase 1: Cerdulatinib 100 mg QD 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. | 3 |
| Phase 1: Cerdulatinib 45 mg BID 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. | 5 |
| Phase 2a: Cerdulatinib (FL Cohort) 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. | 42 |
| Phase 2a: Cerdulatinib (MZL/WM Cohort) 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. | 12 |
| Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) 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. | 26 |
| Phase 2a: Cerdulatinib (aNHL Cohort) 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. | 6 |
| Phase 2a: Cerdulatinib (CLL/SLL Cohort) 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. | 28 |
| Phase 2a: Cerdulatinib (PTCL Cohort) 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. | 65 |
| Phase 2a: Cerdulatinib (CTCL Cohort) 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. | 41 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 | 2 | 7 | 3 | 17 | 6 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Informed consent withdrawn | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other than specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 4 | 4 |
| Overall Study | Participants rolled over into expanded access program (NCT04757259) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 7 | 0 | 0 | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 1 | 0 | 1 | 4 | 2 |
| Overall Study | Progressive disease | 3 | 4 | 4 | 3 | 2 | 3 | 3 | 6 | 2 | 2 | 13 | 8 | 7 | 3 | 6 | 44 | 28 |
| Overall Study | Protocol violation/noncompliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Rolled over to Phase 2a | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 2 | 0 | 4 | 3 | 0 |
Baseline characteristics
| Characteristic | Total | 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 15 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) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 143 Participants | 5 Participants | 4 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 5 Participants | 2 Participants | 4 Participants | 19 Participants | 5 Participants | 13 Participants | 4 Participants | 20 Participants | 32 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 120 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 23 Participants | 7 Participants | 13 Participants | 2 Participants | 8 Participants | 33 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 232 Participants | 6 Participants | 7 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 6 Participants | 3 Participants | 3 Participants | 37 Participants | 10 Participants | 24 Participants | 5 Participants | 26 Participants | 53 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 10 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 211 Participants | 6 Participants | 7 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 4 Participants | 36 Participants | 11 Participants | 22 Participants | 6 Participants | 23 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Female | 97 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 16 Participants | 4 Participants | 9 Participants | 1 Participants | 12 Participants | 24 Participants | 18 Participants |
| Sex: Female, Male Male | 166 Participants | 4 Participants | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 26 Participants | 8 Participants | 17 Participants | 5 Participants | 16 Participants | 41 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 7 | 0 / 3 | 1 / 3 | 0 / 3 | 0 / 4 | 0 / 6 | 1 / 3 | 1 / 5 | 0 / 42 | 0 / 12 | 0 / 26 | 0 / 6 | 0 / 28 | 1 / 65 | 0 / 41 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 7 / 7 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 3 / 3 | 5 / 5 | 42 / 42 | 12 / 12 | 26 / 26 | 6 / 6 | 28 / 28 | 65 / 65 | 41 / 41 |
| serious Total, serious adverse events | 0 / 3 | 2 / 6 | 4 / 7 | 0 / 3 | 1 / 3 | 0 / 3 | 2 / 4 | 2 / 6 | 2 / 3 | 3 / 5 | 22 / 42 | 2 / 12 | 7 / 26 | 3 / 6 | 17 / 28 | 42 / 65 | 21 / 41 |
Outcome results
Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT)
DLT was defined as any of the following toxicities, possibly or probably related to cerdulatinib, and clinically significant (in the judgement of Investigator): -Febrile neutropenia (absolute neutrophil count \<1000/microliter \[μL\] and temperature ≥38.5°Celcius). -Grade 4 neutropenia for \>5 days. -Grade 4 thrombocytopenia with or without bleeding. -Grade 3 thrombocytopenia with bleeding. -Grade 4 anemia, unexplained by underlying disease. -Grade 3 or greater nausea, vomiting, or diarrhea if persistent despite optimal antiemetic or anti-diarrheal therapy. -Grade 3 or greater increase in transaminases lasting \>5 days. -Grade 3 or greater fatigue persisting \>7 days in absence of any other underlying cause. -Any other Grade 3 or greater non-hematologic toxicity (except fatigue as noted above) considered clinically significant by Investigator. -Toxicity of any grade resulting in dose delay of \>7 days. -Toxicity resulting in study drug discontinuation prior to completion of Cycle 1.
Time frame: Baseline up to Day 28 of Cycle 1 (cycle = 21 days or 28 days)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 0 Participants |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 1 Participants |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1: Number of Participants With a Dose Limiting Toxicity (DLT) | 2 Participants |
Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
CR included: -Via a positron emission tomography (PET)/computed tomography (CT) scan, score of 1 (no uptake above background), 2 (uptake of \<mediastinum), or 3 (uptake of \>mediastinum but \<liver) for lymph nodes and extralymphatic sites; no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. -Via CT scan, target nodes/nodal masses regressed to \<1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; organ enlargement has regressed to normal; and bone marrow was normal by morphology and if indeterminate, immunohistochemistry was negative. PR included: -Via a PET/CT scan, score of 4 (uptake of moderately \>liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual masses of any size. -Via CT scan, \>50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 12 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 6 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 15 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 5 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 14 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 2a: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 7 Participants |
Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE)
An AE is any untoward medical occurrence, which may or may not have a causal relationship to the study drug, including: unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug; any newly occurring event or exacerbation of previous condition (for example, increase in severity or frequency) since the administration of study drug; recurrence of an intermittent medical condition not present at baseline; any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug; and AEs related to a study intervention. An SAE is an AE that is fatal, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or a congenital anomaly/birth defect.
Time frame: Baseline up to End of Study (up to 30 days after last dose in Cycle 10 [cycle = up to 28 days])
Population: The Safety Analysis Population included participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 3 Participants |
| Phase 1: Cerdulatinib 15 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 0 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 6 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 2 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 7 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 4 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 3 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 0 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 1 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 3 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 0 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 3 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 4 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 2 Participants |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 6 Participants |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 2 Participants |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 3 Participants |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 2 Participants |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 5 Participants |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 3 Participants |
| Phase 2a: Cerdulatinib (FL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 42 Participants |
| Phase 2a: Cerdulatinib (FL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 22 Participants |
| Phase 2a: Cerdulatinib (MZL/WM Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 2 Participants |
| Phase 2a: Cerdulatinib (MZL/WM Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 12 Participants |
| Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 7 Participants |
| Phase 2a: Cerdulatinib Plus Rituximab (FL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 26 Participants |
| Phase 2a: Cerdulatinib (aNHL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 6 Participants |
| Phase 2a: Cerdulatinib (aNHL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 3 Participants |
| Phase 2a: Cerdulatinib (CLL/SLL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 28 Participants |
| Phase 2a: Cerdulatinib (CLL/SLL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 17 Participants |
| Phase 2a: Cerdulatinib (PTCL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 65 Participants |
| Phase 2a: Cerdulatinib (PTCL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 42 Participants |
| Phase 2a: Cerdulatinib (CTCL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | AE | 41 Participants |
| Phase 2a: Cerdulatinib (CTCL Cohort) | Phase 1 and Phase 2: Number of Participants With an Adverse Event (AE) or a Serious Adverse Event (SAE) | SAE | 21 Participants |
Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib
Time frame: Cycle (C)1 Day (D)1: predose (0), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, and 72 hours postdose (except 15mg QD); C1D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (15mg QD); C2D1: 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose (all doses)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 1321 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 140.21 |
| Phase 1: Cerdulatinib 15 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 709.6 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 37.823 |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 1900 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 918.79 |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 1040 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 347.34 |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 6804 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 3065.6 |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 1826 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 713.67 |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 601.4 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 118.04 |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 2129 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 533.14 |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 6313 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 166.81 |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 2064 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 666.52 |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 674.5 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 113.34 |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 2779 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 458.94 |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 5871 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 3685.1 |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 2465 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 305.7 |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 2 | 6215 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 249.64 |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 2719 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 1208.2 |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 2758 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 969.37 |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Cerdulatinib | Day 1 of Cycle 1 | 1335 hours*nanograms/milliliter (h*ng/mL) | Standard Deviation 530.56 |
Phase 1: Number of Participants Achieving Clinical Benefit
Clinical benefit was defined as achieving stable disease (SD) or better, as assessed by the Investigator. SD included: -Via a PET/CT scan, a score of 4 (uptake of moderately \>liver) or 5 (uptake markedly higher than liver and/or new lesions) with no significant change in FDG uptake from baseline at interim or end of treatment; no new lesions; and no change from baseline in bone marrow. -Via CT scan, \<50% decrease from baseline in sum of products of the greatest perpendicular diameters (SPD) of up to 6 dominant, measurable nodes and extranodal sites; no increase consistent with progression in nonmeasured lesions or organ enlargement; and no new lesions.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 2 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 4 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 4 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1: Number of Participants Achieving Clinical Benefit | 1 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 1 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1: Number of Participants Achieving Clinical Benefit | 0 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 2 Participants |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 2 Participants |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1: Number of Participants Achieving Clinical Benefit | 1 Participants |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1: Number of Participants Achieving Clinical Benefit | 1 Participants |
Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator
CR included: -Via a PET/CT scan, score of 1 (no uptake above background), 2 (uptake of \<mediastinum), or 3 (uptake of \>mediastinum but \<liver) for lymph nodes and extralymphatic sites; no new lesions; and no evidence of FDG-avid disease in bone marrow. -Via CT scan, target nodes/nodal masses regressed to \<1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement has regressed to normal; and bone marrow was normal by morphology and if indeterminate, immunohistochemistry was negative. PR included: -Via a PET/CT scan, a score of 4 (uptake of moderately \>liver) or 5 (uptake markedly higher than liver and/or new lesions) with reduced uptake compared with baseline and residual masses of any size. -Via CT scan, \>50% decrease in the sum of the product of perpendicular diameters for multiple lesion of up to 6 target measurable nodes and extranodal sites.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 21 days or 28 days])
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 1 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 1 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 65 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 1 Participants |
| Phase 1: Cerdulatinib 100 mg QD | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 0 Participants |
| Phase 1: Cerdulatinib 45 mg BID | Phase 1: Number of Participants Achieving Overall Response Rate (Partial Response [PR] Plus Complete Response [CR]) as Assessed by the Investigator | 2 Participants |
Phase 2a: Median Time to Progression-Free Survival (PFS)
PFS=(first documentation of disease progression \[DP\] or death \[whichever occurred first\]-study drug first dose date+1)/30.4375 in months. PFS right censored for 1 of these conditions: 1) no baseline disease assessments; 2) starting new anticancer therapy before documented DP/death; 3) DP/death immediately after \>6 months since last disease assessment (or \>12 months if after last cycle); & alive without documented DP. 95% confidence interval estimated using Brookmeyer method. DP included: -Via a PET/CT scan, score of 4 (uptake of moderately \>liver) or 5 (uptake markedly higher than liver and/or new lesions) with uptake increase in intensity, new FDG-avid foci, & no nonmeasured lesions. -Via CT, abnormal individual node/lesion with significant LDi or shortest axis perpendicular to LDi increase; prior splenomegaly, \>50% splenic length increase; if no prior splenomegaly, ≥2 cm splenic length increase; new or recurrent splenomegaly; new/clear progression of preexisting nonmeasured lesions.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 2a: Median Time to Progression-Free Survival (PFS) | 12.68 months |
| Phase 1: Cerdulatinib 30 mg QD | Phase 2a: Median Time to Progression-Free Survival (PFS) | 3.61 months |
| Phase 1: Cerdulatinib 45 mg QD | Phase 2a: Median Time to Progression-Free Survival (PFS) | 18.33 months |
| Phase 1: Cerdulatinib 15 mg BID | Phase 2a: Median Time to Progression-Free Survival (PFS) | NA months |
| Phase 1: Cerdulatinib 40 mg QD | Phase 2a: Median Time to Progression-Free Survival (PFS) | 4.57 months |
| Phase 1: Cerdulatinib 20 mg BID | Phase 2a: Median Time to Progression-Free Survival (PFS) | 1.18 months |
| Phase 1: Cerdulatinib 50 mg QD | Phase 2a: Median Time to Progression-Free Survival (PFS) | 3.45 months |
Phase 2a: Number of Participants Achieving Clinical Benefit
Clinical benefit was defined as achieving SD or better, as assessed by the Investigator. SD included: -Via a PET/CT scan, a score of 4 (uptake of moderately \>liver) or 5 (uptake markedly higher than liver and/or new lesions) with no significant change in FDG uptake from baseline at interim or end of treatment; no new lesions; and no change from baseline in bone marrow. -Via CT scan, \<50% decrease from baseline in sum of products of the greatest perpendicular diameters (SPD) of up to 6 dominant, measurable nodes and extranodal sites; no increase consistent with progression in nonmeasured lesions or organ enlargement; and no new lesions.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 2a: Number of Participants Achieving Clinical Benefit | 19 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 2a: Number of Participants Achieving Clinical Benefit | 8 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 2a: Number of Participants Achieving Clinical Benefit | 16 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 2a: Number of Participants Achieving Clinical Benefit | 10 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 2a: Number of Participants Achieving Clinical Benefit | 17 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 2a: Number of Participants Achieving Clinical Benefit | 2 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 2a: Number of Participants Achieving Clinical Benefit | 16 Participants |
Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR)
DMR was defined as achieving a ≥50% decrease from baseline in the SPD of the target nodal and extranodal lesions. SPD at a visit was considered missing if any target lesion was not evaluated.
Time frame: Baseline up to End of Treatment (up to last day of Cycle 10 [cycle = 28 days])
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Cerdulatinib 15 mg QD | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 14 Participants |
| Phase 1: Cerdulatinib 30 mg QD | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 5 Participants |
| Phase 1: Cerdulatinib 45 mg QD | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 14 Participants |
| Phase 1: Cerdulatinib 15 mg BID | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 7 Participants |
| Phase 1: Cerdulatinib 40 mg QD | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 15 Participants |
| Phase 1: Cerdulatinib 20 mg BID | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 1 Participants |
| Phase 1: Cerdulatinib 50 mg QD | Phase 2a: Number of Participants Achieving Dominant Mass Response (DMR) | 5 Participants |