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New treatment option for Non Hodgkin Lymphoma
Official title Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.
ClinicalTrials.gov ID: NCT04771572
What this study is testing
What is LP-118?
LP-118 is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for non hodgkin lymphoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is a Phase 1, multi-center, open-label study with a dose-escalation phase (Phase 1a) and a cohort expansion phase (Phase 1b), to evaluate the safety, tolerability, and PK profile of LP-118 under a once daily oral dosing schedule in up to 100 subjects.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 13 and older
You may be able to join if
- Male or female people, ≥ 18 years of age at the time of Screening with the following exception as outlined below: -For T cell and B cell ALL people...
- Eligible subject must have an advanced hematologic malignancy including: Group 1: Group 1a
- Relapsed or refractory low risk tumor lysis CLL/SLL people (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm) who have received at least two prior...
- For CLL/SLL people who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows washout for 2 days as these people, progress...
- Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that...
You likely can't join if
- A subject will not be eligible for study participation if he/she meets any of the following criteria.
- people who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or...
- Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed...
- Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;
- Continuation of maintenance therapy in patients with adequately treated malignancy
- Adequately treated in situ carcinoma of the cervix uteri;
See the full eligibility criteria
Who can join
- Male or female people, ≥ 18 years of age at the time of Screening with the following exception as outlined below: -For T cell and B cell ALL people with age between 13 - 18 years, their body weight shall be ≥ 40 kg.
- Eligible subject must have an advanced hematologic malignancy including: Group 1: Group 1a
- Relapsed or refractory low risk tumor lysis CLL/SLL people (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm) who have received at least two prior therapies. people may also have slowly progressed on irreversible BTK...
- For CLL/SLL people who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows washout for 2 days as these people, progress quickly after treatment discontinuation and then remain eligible...
- Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, people who have no available...
- Morphologically confirmed diagnosis of MDS/MPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory and that, in the opinion of the...
- Chronic myelomonocytic leukemia (CMML) with \<9% blasts;
- Or atypical chronic myeloid leukemia (aCML) with Hgb \> 10g/dL, WBC count \< 50 x 109 cells/L, \<10% immature circulating cells;
- Or MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) with Hgb \> 10g/dL;
- Or myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC)
- CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and/or refractory to prior HMA therapy;
- Relapsed and/or refractory MPN-BP as defined by WHO 2016 revised criteria that is transformed MPN with \>20% myeloid blasts in the peripheral blood or bone marrow, in the opinion of the Investigator, people who have no...
- MDS people with refractory anemia with excess blasts (MDS-EB; subtype MDS-EB-1 or MDS-EB-2) as defined by WHO 2016 revised criteria and/or MDS with high- or very high-risk (risk score \> 4.5) per the Revised...
- Relapsed or refractory AML people (including de novo AML, secondary AML evolving from MDS or MPN or other antecedent hematologic disorder, and therapy-related AML) as defined by WHO 2016 revised criteria, people who...
- Relapsed or refractory low risk tumor lysis NHL (NHL histologies [MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL] are to be included per the 2016 World Health Organization [WHO] criteria) people, must have...
- Low risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) people who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy...
- Low risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;
- Relapsed or refractory multiple myeloma (MM) people who have received a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 and have no treatment options available known to provide clinical...
- Low risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) people who have received one therapy for this and are relapsed or refractory; Group 1d
- Relapsed or refractory ALL with dexamethasone run-in [5 days, dexamethasone 10mg/m2 (divided BID)];
- Or r/r ALL in remission but with detectable MRD (MRD +) by any detection method per institution standard of practice;
- IT chemo (per institutional SOC) is permitted prior to LP-118 C1D1 dosing, and then concomitantly on treatment if in best interest of the subject;
- Relapsed or refractory ALL people with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and/or tyrosine kinase inhibitors including bosutinib, dasatinib...
- Relapsed or refractory ALL people with age between 13 - 18 years and have body weight ≥ 40kg, ALL people with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy...
- Relapsed or refractory intermediate and high risk tumor lysis CLL/SLL people who have received at least two prior therapies;
- Relapsed or refractory intermediate and high risk tumor lysis NHL (NHL histologies [MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL] are to be included per the 2016 World Health Organization [WHO] criteria) people, must...
- Intermediate and high risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) people who must have received at least one prior systemic therapy for the transformed lymphoma (unless...
- Intermediate and high risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;
- Intermediate and high risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) people who have received one therapy for this and are relapsed or refractory;
- For Group 1d ALL people only, white blood cell (WBC) count ≤ 25 × 109 cells/L at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
- Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.
- Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows: Bone marrow criteria:
- Group 1 (r/r low risk tumor lysis CLL/SLL (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm), NHL, RT, MM, T-PLL):
- Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (An exception is for people with an ANC\<1 x 109/L and bone marrow heavily infiltrated with underlying disease)
- Platelets ≥ 50 x 109/L on day of screening (entry platelet count must be independent of transfusion with 14 days of screening);
- Hemostasis criteria: Activated partial thromboplastin time (APPT) and prothrombin time (PT) ≤ 1.5 × the upper limit of normal (ULN);
- Renal function criteria: Serum creatinine ≤ ULN (per local institution reference range) or Calculated creatinine clearance (Cr Cl) ≥ 60 mL/min using 24-hour CrCl OR by Cockcroft-Gault formula using actual body weight.
- Hepatic function criteria: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; bilirubin ≤ 1.5 × ULN (except people with Gilbert's Syndrome, who may have a bilirubin \> 1.5 × ULN, per...
- Females of childbearing potential (i.e., non-postmenopausal for at least 2 years or surgically sterile) and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s)...
- Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable;
- Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy;
- Intrauterine device;
- Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) associated with inhibition of ovulation initiated for at least 1 month prior to study drug administration.
- Females of childbearing potential must have a negative pregnancy result as follows:
- At Screening on a serum sample obtained within 7 days prior to the first study drug administration, and
- Prior to dosing on a urine or serum sample obtained on the first day of study drug administration if ithas been \> 7 days since obtaining the serum pregnancy test results in Screening.
- If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation
- Male people must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.
- Subject must be able to understand and voluntarily sign and date an informed consent form (ICF), approved by an IRB, prior to any protocol-related procedures.
What rules you out
- A subject will not be eligible for study participation if he/she meets any of the following criteria.
- people who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or people on immunosuppressive therapy post-HSCT at the time of...
- Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below.
- Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;
- Continuation of maintenance therapy in patients with adequately treated malignancy
- Adequately treated in situ carcinoma of the cervix uteri;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment
- Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous...
- Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \< 20 mg/day prednisone equivalent according to...
- For MF people who come off JAK2 antagonists, allow washout for 2 days as these subject's progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease...
- people in need of immediate cytoreduction should be excluded.
- Any investigational therapy.
- Live vaccines
- Subject has received the following medications, therapies, or natural products within 7 days prior to the first dose of LP-118:
- Cytochrome P450, family 3, subfamily A (CYP3A) strong inhibitors (itraconazole, etc.), or substrates (Appendix 19);
- Subject has received strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers within 14 days prior to the first dose of LP-118 (Appendix 19);
- Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit;
- There is a 28-day washout period required for people who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment, per discussion...
- Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect...
- Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula [QTcF = QT/RR (1/3)])), a cardiovascular disability status of New York Heart Association...
- Subject has significant a history of congenital long QT syndrome or Torsades de Pointes (TdP), uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke, or intracranial hemorrhage...
- Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled active systemic infection (bacterial, fungal, viral);
- Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HbsAg positive, or HbcAb positive with detectable HBV DNA load; active hepatitis C defined...
- Unexplained fever \> 38.5°C within 7 days prior to the first dose of study drug administration (at the discretion of the Investigator if the fever is considered attributed to the subject's malignancy or an explained...
- A female subject is pregnant or breast-feeding.
- Subject incapacity to swallow oral medications, with any malabsorption condition, known dysphagia, short-gut syndrome, gastroparesis, or other conditions that, in the opinion of the Investigator, may limit the ingestion...
- people with known and active central nervous system (CNS) involvement at Screening.
- people with known hypersensitivity to any of the components of LP-118 (see Investigators Brochure for a list of components).
- people who are taking QT-prolonging drugs that are known to cause Torsades de Pointes (TdP) (See Appendix 17 for the list of medications that are associated with TdP). In the event a prohibited medication might cause...
- Major surgery within 14 days prior to the first dose of study drug.
The study team makes the final eligibility decision.
Where it's taking place
- Chicago, Illinois, United States
- Boston, Massachusetts, United States
- Chapel Hill, North Carolina, United States
- Cincinnati, Ohio, United States
- Columbus, Ohio, United States
- Houston, Texas, United States
- Salt Lake City, Utah, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 13 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Chicago, Illinois, United States; Boston, Massachusetts, United States; Chapel Hill, North Carolina, United States; Cincinnati, Ohio, United States; Columbus, Ohio, United States; Houston, Texas, United States and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.