Phase 1/2 Study of TP-0903 (an Inhibitor of AXL Kinase) in Patients With Previously Treated CLL

Sponsor
Sumitomo Pharma Oncology, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT03572634
Collaborator
(none)
3
Enrollment
6
Locations
2
Arms
7.4
Actual Duration (Months)
0.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

TP-0903 is an inhibitor of AXL kinase. TP-0903 has shown potent inhibition of AXL kinase and other TAM family members in a biochemical kinase assay. TP-0903 demonstrates corresponding activity in cancer cell lines and mouse xenograft efficacy models. TP-0903 is shown to block cancer cell epithelial-to-mesenchymal transitions. AXL was identified as a potential therapeutic target in chronic lymphocytic leukemia (CLL). TP 0903 was shown to induce apoptosis in CLL B-cells taken directly from patients.TP-0903 was equally potent against CLL cells regardless of risk-factor.

TP-0903 is a novel oral inhibitor that targets AXL kinase and reverses the mesenchymal phenotype associated with advanced cancers. TP-0903 has demonstrated profound single agent activity in CLL B cells taken directly from patients even if the patient has high risk factors (ie, 17p/P53 deletions) or progressed on other agents (ie, ibrutinib). TP-0903 is currently being evaluated in patients with refractory solid tumors (TP-0903-101). This proposed study is designed to identify the maximum tolerated dose (MTD), safety profile and recommended Phase 2 dose (RP2D) of TP-0903 in patients with previously treated CLL. Treatment cycles may be repeated if the patient continues to show benefit and if TP-0903 is reasonably well tolerated.

The study will investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TP-0903.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: TP-0903
  • Combination Product: TP-0903 and ibrutinib combination therapy
Phase 1/Phase 2

Detailed Description

This is a combined Phase 1/2 study of oral TP-0903 in patients with previously treated CLL/SLL. In both Phase 1 and Phase 2, study participants will be assigned to one of two defined patient groups:

  • Group 1 (TP-0903 monotherapy): Patients with CLL/SLL who are intolerant to, or have progressed on, B-cell receptor antagonists and/or BCL-2 antagonists

  • Group 2 (TP-0903 and ibrutinib combination therapy): Patients with CLL/SLL who have progressed on ibrutinib yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient.

Both groups of patients will be treated identically with TP 0903 and will undergo the same study assessments.

Phase 1 Patients will be enrolled in Group 1 and Group 2 in cohorts of 3 to 6 patients simultaneously. Group 2 will start at one dose level below the Group 1 starting dose. In each group, escalation of the TP-0903 dose will follow a standard 3+3 design with sequential cohorts of three patients treated with incrementally higher doses of TP 0903 until a dose-limiting toxicity (DLT) is observed and the maximum tolerated dose (MTD) is established. In the absence of DLTs, the dose will be increased using a modified Fibonacci dose escalation scheme.

Once the MTD or preliminary RP2D is identified, an expansion cohort of up to 6 patients will be enrolled in each patient group to confirm safety/suitability of the preliminary RP2D, to collect additional biomarker data, and to further explore efficacy.

It is expected that up to 27 patients will be enrolled in each patient group for a total of up to 54 patients (TP-0903 monotherapy and combination therapy with ibrutinib).

Additional dose levels, schedules, or disease indications of TP 0903 may be explored, as appropriate, based on the modulation of key biomarkers and the safety profile and clinical signals of activity.

Phase 2 In Phase 2, patients will be enrolled in Group 1 (TP 0903 monotherapy) and Group 2 (TP-0903 combination therapy with ibrutinib) based on the Simon 2 stage design. In Stage 1, up to 13 patients will be enrolled into each patient group (total of 26 patients). If there are no responses among these 13 patients in each group, the study will be stopped. Otherwise, Stage 2 will open to enroll 14 additional patients in each group for a total of 27 patients per group. If 4 or more responses are observed among 27 patients, the conclusion will be that the study treatment is worthy of further investigation.

If both patient groups enroll through Stage 2, it is anticipated that the total enrollment for Phase 2 will be 54 patients.

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Adult patients with CLL/SLL who: are intolerant to, or have had progressive disease on B-cell receptor antagonists, BCL-2 antagonists or other investigational treatments for CLL/SLL (Group 1-TP 0903 monotherapy); or have progression of disease on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient (Group 2-TP-0903 and ibrutinib combination therapy)Adult patients with CLL/SLL who:are intolerant to, or have had progressive disease on B-cell receptor antagonists, BCL-2 antagonists or other investigational treatments for CLL/SLL (Group 1-TP 0903 monotherapy); or have progression of disease on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient (Group 2-TP-0903 and ibrutinib combination therapy)
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Combined Phase 1/2 Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of TP-0903 in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Jun 10, 2019
Actual Primary Completion Date :
Jan 21, 2020
Actual Study Completion Date :
Jan 21, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Group 1-TP 0903 monotherapy

Adult patients with CLL/SLL who: are intolerant to, or have had progressive disease on B-cell receptor antagonists, BCL-2 antagonists or other investigational treatments for CLL/SLL

Drug: TP-0903
Monotherapy: PHASE 1: TP-0903 will be a 25 mg flat dose. The study drug will be administered orally once daily for 28 days (each cycle is 28 days; no drug-free period). Patients may continue to receive TP-0903 in 28-day cycles at the same dose given during Cycle 1 until they experience unacceptable toxicity or unequivocal disease progression. No intrapatient escalation of the TP-0903 dose is permitted. PHASE 2: The starting dose of TP-0903 will be the RP2D determined during Phase 1. TP 0903 will be administered orally at a fixed dose once daily for 28 days (each cycle is 28 days; no drug-free period) with repeated cycles permitted until a patient experiences unacceptable toxicity or unequivocal disease progression.

Experimental: Group 2-TP-0903 and ibrutinib combination therapy

Adult patients with CLL/SLL who: have progression of disease on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient

Combination Product: TP-0903 and ibrutinib combination therapy
Combination therapy: PHASE 1: TP-0903 and ibrutinib combination therapy: The starting dose of TP-0903 will be a 20 mg flat dose. TP-0903 will be administered orally once daily for 28 days (each cycle is 28 days; no drug-free period). Patients will also receive ibrutinib at the same dose that they were receiving immediately prior to study enrollment. Patients should continue with the combination of ibrutinib and TP-0903 for at least 3 months after study start. PHASE 2: The starting dose of TP-0903 will be the RP2D determined during Phase 1. Patients will also receive ibrutinib at the same dose that they were receiving immediately prior to study enrollment. Both TP 0903 and ibrutinib will be administered orally at fixed doses once daily for 28 days (each cycle is 28 days; no drug-free period).

Outcome Measures

Primary Outcome Measures

  1. PHASE 1: Incidence of Dose-limiting Toxicities (DLTs) and Treatment Emergent Adverse Events. [28 days]

    A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment

  2. PHASE 2: ORR in the Two Defined Patient Groups According to Guidelines Set Forth by the 2018 IWCLL [3 months]

    Objective Response Rate ([ORR], ie, rate of complete response [CR] plus rate of partial response [PR] in the defined patient groups according to guidelines set forth by the 2018 International Workshop on CLL (IWCLL)

Secondary Outcome Measures

  1. PHASE 1: Area Under the Plasma Concentration-time Curve From Zero to Infinity of Oral TP-0903 in the Defined Patient Groups [28 days]

    Blood samples will be collected from patients so that derived PK parameters by non-compartment analysis may be conducted on Cycle 1

  2. PHASE 1: Peak Plasma Concentration (Cmax) of Oral TP-0903 in the Defined Patient Groups [28 days]

    Blood samples will be collected from patients so that derived PK parameters by non-compartment analysis may be conducted on Cycle 1

  3. PHASE 2: To Determine the Duration of Response [2 years]

    Time from tumor response to disease progression

  4. PHASE 2: Rate of Overall Survival [2 years]

    The time from first dose to objective tumor progression or death

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Be ≥18 years old

  2. Have an established, pathologically confirmed diagnoses of CLL/ Small Lymphocytic Lymphoma (SLL) requiring therapy according to the 2018 IWCLL guidelines

  3. Have received at least one prior therapy for CLL/SLL and can be classified in one of two patient groups:

  • Group 1 (TP-0903 monotherapy): Patients with CLL/SLL who are intolerant to, or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments for CLL/SLL

  • Group 2 (TP-0903 and ibrutinib combination therapy): Patients with CLL/SLL who have progressed on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient

  1. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

  2. Have adequate hematologic function:

  • Absolute neutrophil count (ANC) ≥500/µL

  • Platelet count ≥30,000/µL

  • Hemoglobin ≥8 g/dL in the absence of transfusions within the previous 2 weeks

  1. Have adequate organ function:
  • Creatinine clearance ≥30 mL/min

  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤2.5 × upper limit of normal (ULN)

  • Have a total bilirubin level ≤1.5 × ULN (unless secondary to Gilbert syndrome, hemolysis, or leukemia)

  1. Have acceptable coagulation status:

• Activated partial thromboplastin (aPTT) and prothrombin time (PT) ≤1.5 × ULN

  1. Have a negative pregnancy test (if female of childbearing potential)

  2. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation and for at least 30 days after the last study drug dose. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.

  3. Have read and signed the Institutional Review Board (IRB) approved informed consent form (ICF) prior to any study related procedure. (In the event that the patient is rescreened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.)

  4. Are able to comply with the requirements of the entire study

Exclusion Criteria:
  1. Have undergone prior autologous or allogeneic stem cell transplant within ≤3 months, have not recovered from transplant associated toxicities, or requires graft versus host immunosuppressive therapy

  2. Have known central nervous system (CNS) involvement

  3. Have Richter's transformation of CLL

  4. Have received any monoclonal antibody therapy directed at treatment of the patient's malignancy within 2 weeks prior to anticipated first dose

  5. Have received any anticancer therapy including chemotherapy, radiotherapy, or an investigational anticancer drug within less than 5 half lives of the last dose of that treatment

• This exclusion criterion is not applicable to patients requiring continuation on ibrutinib. (Note: Certain patients with a rapidly rising white blood cell count while on ibrutinib may need to remain on this drug for medical reasons. These patients will need to be approved by the Medical Monitor and treated in accordance with the protocol.)

  1. Have received >20 mg/day of prednisone and 0.1 mg/day of mineralocorticoids within 7 days prior to anticipated first dose

  2. Have a corrected QT interval of >450 msec (males) and >470 msec (females) using Fridericia's correction formula

  3. Have a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease or any other medical condition that, in the opinion of the Investigator, would adversely affect his/her participation in the study

  4. Are pregnant and/or nursing, or refuse to use appropriate contraceptives during the course of the study and for at least 30 days after the last dose of study drug

  5. History of another malignancy in the last 5 years except for the following adequately treated:

  • Local basal cell or squamous cell carcinoma of the skin

  • Carcinoma in situ of the cervix or breast

  • Papillary, noninvasive bladder cancer

  • Early stage prostate cancer for which observation is clinically indicated

  • Other Stage 1 or 2 cancers currently in complete remission

  • Any other cancer that has been in complete remission for 2 years or surgically cured. Medical Monitor may be contacted for additional determination of acceptable prior cancer history

  1. Have known gastrointestinal disorders (eg, malabsorption syndrome), complications (eg, dysphagia), or surgery that could make consumption or absorption of oral medications problematic

  2. Have an uncontrolled systemic infection (viral, bacterial, or fungal) or fever and neutropenia within 7 days prior to anticipated first dose

  3. Have active and uncontrolled autoimmune cytopenias for 2 or more weeks including autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)

  4. Have received prior therapy with an AXL inhibitor

  5. Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation

  6. Are unwilling or unable to comply with procedures required in this protocol

  7. Have a history of severe adverse reaction (eg. hypersensitivity reaction, anaphylaxis) to sulfonamides

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Mayo Clinic ArizonaPhoenixArizonaUnited States85054
2Mayo Clinic FloridaJacksonvilleFloridaUnited States32224
3Mayo Clinic RochesterRochesterMinnesotaUnited States55905
4Washington University - St LouisSaint LouisMissouriUnited States63130
5Cornell UniversityNew YorkNew YorkUnited States10065
6Duke UniversityDurhamNorth CarolinaUnited States27705

Sponsors and Collaborators

  • Sumitomo Pharma Oncology, Inc.

Investigators

  • Study Director: Phillip Komarnitsky, Sumitomo Pharma Oncology, Inc.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Sumitomo Pharma Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT03572634
Other Study ID Numbers:
  • TP-0903-102
First Posted:
Jun 28, 2018
Last Update Posted:
Apr 6, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Sumitomo Pharma Oncology, Inc.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details3 patients at 2 sites; 6 study sites were initiated; study sites were medical clinics Recruitment started: Jan 21, 2019 Recruitment ended: January 21, 2020
Pre-assignment DetailGroup 1 (TP-0903 monotherapy): Patients with CLL/SLL who are intolerant to, or have progressed on, B-cell receptor antagonists and/or BCL-2 antagonists Group 2 (TP-0903 and ibrutinib combination). Group 2 will start at one dose level below the Group 1 starting dose.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Period Title: Overall Study
STARTED12
COMPLETED12
NOT COMPLETED00

Baseline Characteristics

Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)Total
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients with CLL/SLL who had progressed on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.Total of all reporting groups
Overall Participants123
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
0
0%
1
50%
1
33.3%
>=65 years
1
100%
1
50%
2
66.7%
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
0
0%
Male
1
100%
2
100%
3
100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
White
1
100%
2
100%
3
100%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
United States
1
100%
2
100%
3
100%

Outcome Measures

1. Primary Outcome
TitlePHASE 1: Incidence of Dose-limiting Toxicities (DLTs) and Treatment Emergent Adverse Events.
DescriptionA DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment
Time Frame28 days

Outcome Measure Data

Analysis Population Description
Primary and secondary efficacy endpoints were not analyzed via statistical methods due to low enrollment in Phase 1 and no enrollment in Phase 2.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients with CLL/SLL who had progressed on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00
2. Primary Outcome
TitlePHASE 2: ORR in the Two Defined Patient Groups According to Guidelines Set Forth by the 2018 IWCLL
DescriptionObjective Response Rate ([ORR], ie, rate of complete response [CR] plus rate of partial response [PR] in the defined patient groups according to guidelines set forth by the 2018 International Workshop on CLL (IWCLL)
Time Frame3 months

Outcome Measure Data

Analysis Population Description
Primary and secondary efficacy endpoints were not analyzed via statistical methods due to low enrollment in Phase 1 and no enrollment in Phase 2.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00
3. Secondary Outcome
TitlePHASE 1: Area Under the Plasma Concentration-time Curve From Zero to Infinity of Oral TP-0903 in the Defined Patient Groups
DescriptionBlood samples will be collected from patients so that derived PK parameters by non-compartment analysis may be conducted on Cycle 1
Time Frame28 days

Outcome Measure Data

Analysis Population Description
The study was stopped prematurely due to low enrollment across the 6 investigative sites. Efficacy endpoints could not be reached, and PK and PD test results could not be evaluated due to low sample size.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00
4. Secondary Outcome
TitlePHASE 1: Peak Plasma Concentration (Cmax) of Oral TP-0903 in the Defined Patient Groups
DescriptionBlood samples will be collected from patients so that derived PK parameters by non-compartment analysis may be conducted on Cycle 1
Time Frame28 days

Outcome Measure Data

Analysis Population Description
The study was stopped prematurely due to low enrollment across the 6 investigative sites. Efficacy endpoints could not be reached, and PK and PD test results could not be evaluated due to low sample size.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00
5. Secondary Outcome
TitlePHASE 2: To Determine the Duration of Response
DescriptionTime from tumor response to disease progression
Time Frame2 years

Outcome Measure Data

Analysis Population Description
The study was stopped prematurely due to early discontinuation of the study as a result of low enrollment. Efficacy endpoints could not be reached, and PK and PD test results could not be evaluated due to low sample size. 1 patient was enrolled in the Monotherapy group, 2 patients were enrolled in the Combination therapy group; 3 patients in total were enrolled in the study.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00
6. Secondary Outcome
TitlePHASE 2: Rate of Overall Survival
DescriptionThe time from first dose to objective tumor progression or death
Time Frame2 years

Outcome Measure Data

Analysis Population Description
The study was stopped prematurely due to low enrollment across the 6 investigative sites. Efficacy endpoints could not be reached, and PK and PD test results could not be evaluated due to low sample size.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
Measure Participants00

Adverse Events

Time FrameTreatment-emergent adverse events (TEAEs) were defined as all AEs that begin on or after the date of first dose of study drug. All patients in the study participated in Phase 1; a 30 day follow-up visit as part of the protocol noted patients undergo a safety evaluation in which the patient's condition during the 30 days after the last dose of study drug can be assessed. There is a visit window of up to 14 days after completion of 30 days from the last dose (ie, within 45 days after last dose).
Adverse Event Reporting Description An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not related to the drug product.
Arm/Group TitleTP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Arm/Group DescriptionPatients who are intolerant to, or have had progressive disease on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments. This represents phase I, phase II never occurred and dose escalation did not occur.Patients who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient. This represents phase I, phase II never occurred and dose escalation did not occur.
All Cause Mortality
TP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/1 (0%) 0/2 (0%)
Serious Adverse Events
TP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/1 (0%) 2/2 (100%)
General disorders
Pyrexia0/1 (0%) 01/2 (50%) 1
Infections and infestations
Lung Infection0/1 (0%) 02/2 (100%) 2
Investigations
Increased Alanine Aminotransferase and Aspartate Aminotransferase levels0/1 (0%) 01/2 (50%) 1
Nervous system disorders
Encephalopathy0/1 (0%) 01/2 (50%) 1
Other (Not Including Serious) Adverse Events
TP-0903 Monotherapy (25mg Dose of TP-0903)TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/1 (100%) 2/2 (100%)
Blood and lymphatic system disorders
Thrombocytopenia0/1 (0%) 01/2 (50%) 1
Leukocytosis0/1 (0%) 01/2 (50%) 1
Leukopenia0/1 (0%) 01/2 (50%) 1
Gastrointestinal disorders
Geographic tongue with aphthous ulcers1/1 (100%) 10/2 (0%) 0
Nausea1/1 (100%) 11/2 (50%) 3
Vomiting0/1 (0%) 01/2 (50%) 1
Diarrhea0/1 (0%) 01/2 (50%) 1
Worsening Intermittent constipation0/1 (0%) 01/2 (50%) 1
General disorders
Pyrexia0/1 (0%) 01/2 (50%) 2
Chills0/1 (0%) 01/2 (50%) 1
Malaise0/1 (0%) 01/2 (50%) 2
Edema Limbs0/1 (0%) 01/2 (50%) 1
Infections and infestations
Nail Infections0/1 (0%) 01/2 (50%) 1
Fungal infection0/1 (0%) 01/2 (50%) 1
Lung Infection0/1 (0%) 02/2 (100%) 2
Skin Infection0/1 (0%) 01/2 (50%) 1
Injury, poisoning and procedural complications
Arthropod bite0/1 (0%) 01/2 (50%) 1
Investigations
Decreased bilirubin level0/1 (0%) 01/2 (50%) 1
Increased alkaline phosphatase level0/1 (0%) 01/2 (50%) 2
Weight gain0/1 (0%) 01/2 (50%) 1
Lymphocyte Count Increase0/1 (0%) 01/2 (50%) 1
Increased Alanine Aminotransferase0/1 (0%) 01/2 (50%) 1
Increased Aspartate Aminotransferase0/1 (0%) 01/2 (50%) 1
Weight loss0/1 (0%) 01/2 (50%) 1
Metabolism and nutrition disorders
Hypoalbuminemia0/1 (0%) 01/2 (50%) 1
Hypocalcemia0/1 (0%) 01/2 (50%) 1
Hyperglycemia0/1 (0%) 01/2 (50%) 1
Hyponatremia0/1 (0%) 01/2 (50%) 1
Hypoglycemia0/1 (0%) 01/2 (50%) 1
Anorexia0/1 (0%) 01/2 (50%) 1
Musculoskeletal and connective tissue disorders
Myalgia0/1 (0%) 01/2 (50%) 1
Nervous system disorders
Headache0/1 (0%) 01/2 (50%) 2
Worsening Encephalopathy0/1 (0%) 01/2 (50%) 1
Worsening peripheral Sensory Neuropathy0/1 (0%) 01/2 (50%) 1
Psychiatric disorders
Delirium0/1 (0%) 01/2 (50%) 1
Insomnia0/1 (0%) 01/2 (50%) 1
Renal and urinary disorders
Urinanry Incontience0/1 (0%) 01/2 (50%) 1
Respiratory, thoracic and mediastinal disorders
Laryngeal hemorrhage0/1 (0%) 01/2 (50%) 1
Cough0/1 (0%) 01/2 (50%) 2
Dsypnea0/1 (0%) 01/2 (50%) 1
Nasal Congestion0/1 (0%) 01/2 (50%) 1
Skin and subcutaneous tissue disorders
Hives1/1 (100%) 10/2 (0%) 0
Purpura0/1 (0%) 01/2 (50%) 1
Hyperhidrosis0/1 (0%) 01/2 (50%) 1
Rash0/1 (0%) 01/2 (50%) 2
Vascular disorders
Worsening Hypertension0/1 (0%) 01/2 (50%) 1

Limitations/Caveats

The study was stopped early (21 January 2020) due to low enrollment.

More Information

Certain Agreements

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

There is NOT 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/TitleSusan Smith
OrganizationSr. Director Drug Development/Clinical Operations
Phone210-414-7702
Emails.smith@toleropharma.com
Responsible Party:
Sumitomo Pharma Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT03572634
Other Study ID Numbers:
  • TP-0903-102
First Posted:
Jun 28, 2018
Last Update Posted:
Apr 6, 2022
Last Verified:
Apr 1, 2022