LP-118 Combination Therapy for Lymphoblastic Leukemia-Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Chicago
Disqualifiers: CNS leukemia, Hepatitis B/C, HIV, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.
Do I need to stop my current medications to join the trial?
The trial information does not specify if you need to stop taking your current medications. However, there is a requirement for a washout period (time without taking certain medications) of 4 half-lives for those who participated in other investigational trials.
What data supports the effectiveness of the drug combination therapy for lymphoblastic leukemia-lymphoma?
Research shows that dexamethasone, a component of the therapy, is more effective than prednisone in treating acute lymphoblastic leukemia (ALL), although it may cause more side effects. Additionally, dexamethasone may help prevent central nervous system relapses in lymphoblastic lymphoma, but it also increases the risk of severe side effects.
12345Is the LP-118 combination therapy generally safe for humans?
Dexamethasone, a component of the LP-118 combination therapy, has been shown to be more effective than prednisone in treating acute lymphoblastic leukemia (ALL) but is associated with greater toxicity, including potential impacts on neuropsychological function and quality of life in children.
16789How is the LP-118 combination drug for lymphoblastic leukemia-lymphoma different from other drugs?
The LP-118 combination drug is unique because it combines multiple agents, including dexamethasone, LP-118, ponatinib, and vincristine, which may offer a novel approach by targeting different pathways in the cancer cells. This combination could potentially enhance treatment effectiveness compared to using these drugs individually.
124610Eligibility Criteria
This trial is for individuals with relapsed or refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL), including various types of non-Hodgkin's lymphoma and leukemia. Participants must have previously undergone treatment without success.Inclusion Criteria
My leukemia or lymphoma has returned or didn't respond to treatment.
I am 18 years old or older.
I have had a hysterectomy, my ovaries removed, or I am confirmed to be post-menopausal.
+9 more
Exclusion Criteria
I have hepatitis B, C, or HIV but my viral load is undetectable.
I do not have any severe uncontrolled health issues like heart or lung problems.
I have not had major surgery in the last 2 weeks.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive LP-118 and ponatinib in combination with standard chemotherapy drugs vincristine, dexamethasone, and methotrexate in 21-day cycles
36 weeks
7 visits in cycle 1, 5 visits per cycle for cycles 2-12
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests LP-118, an experimental drug, in combination with ponatinib, which is already approved for ALL treatment. It also includes vincristine, dexamethasone, and methotrexate to evaluate safety and determine the proper doses.
1Treatment groups
Experimental Treatment
Group I: All Participants (Single Arm)Experimental Treatment5 Interventions
All study participants will receive LP-118 and ponatinib. The initial dose of LP-118 to be tested is 100 mg, and initial dose of ponatinib to be tested is 30 mg. Higher doses of LP-118 will only be tested if the study doctor feels it is safe to do so. A member of the study team will let study participants know which doses they are assigned.
Study drugs will be given in 21-day cycles. There will be 7 study visits in cycle 1 (on Days 1, 5, 6, 7, 15, 22, and 28). LP-118 and ponatinib will be taken at home every day. Dexamethasone will be taken between days 1-7 and days 15-22. For Cycles 2-12, study participants will have 5 study visits per cycle (on Days 1, 8, 15, 22, and 28). On all days, study participants will take LP-118 and ponatinib at home.
Participants in this group will also receive standard of care vincristine, dexamethasone, and methotrexate during study cycles.
Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Dexamethasone for:
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
- Immune system disorders
🇺🇸 Approved in United States as Dexamethasone for:
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
- Neoplastic diseases
- Nervous system disorders
🇨🇦 Approved in Canada as Dexamethasone for:
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
🇯🇵 Approved in Japan as Dexamethasone for:
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Chicago Medicine Comprehensive Cancer CenterChicago, IL
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Who Is Running the Clinical Trial?
University of ChicagoLead Sponsor
References
Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute All Consortium Protocol 00-01. [2021]Dexamethasone is more efficacious than prednisone in the treatment of acute lymphoblastic leukemia (ALL), but has also been associated with greater toxicity. We compared neuropsychological outcomes for patients treated on DFCI ALL Consortium Protocol 00-01, which included a randomized comparison of the two steroid preparations during post-induction therapy in children and adolescents with ALL.
Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group. [2021]Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone.
[Superhigh doses of dexamethasone in treatment of refractory forms of acute lymphoblast leukemia of adults]. [2013]Assessment of high-dose dexamethasone efficacy in combination with standard drugs (adriablastin, vincristin, alpha-asparaginase) in patients with refractory acute lymphoblastic leukemia (ALL).
Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma. [2018]In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0-10.3). The 5-year event-free survival was 82±2% [12 toxic deaths, 5 secondary malignancies, 43 non-response/relapse (central nervous system n=9; all received prednisone during induction)]. The event-free survival rate was 80±5% for patients with precursor B-cell lymphoblastic lymphoma, 82±3% for those with T-cell lymphoblastic lymphoma, and 100% for patients with a mixed phenotype. During induction, significantly more grade III/IV toxicities were observed in patients receiving dexamethasone, resulting in significant treatment delays. The number of toxic deaths did not differ significantly. The only variable associated with outcome was performance status at diagnosis. The 90% event-free survival rate for patients with T-cell lymphoblastic lymphoma shown in study NHL-BFM90 was not replicated, mainly due to more toxic deaths and central nervous system relapses. Dexamethasone in induction may prevent central nervous system relapse more effectively than prednisone but produces a higher burden of toxicity. (#NCT00275106).
Treatment of chronic lymphocytic leukemia and lymphosarcoma with a new chlorambucil ester of prednisolone (Leo 1031) (NSC-134087). [2019]A new chlorambucil ester of prednisolone (LEO 1031) has been evaluated in patients with advanced lymphocytic lymphosarcoma and chronic lymphocytic leukemia. All 11 patients had been previously treated with radiotherapy and/or combination chemotherapy. Three complete remissions and one partial remission were seen in 4/7 lymphocytic lymphosarcoma patients treated with LEO 1031. In the chronic lymphocytic leukemia group, 3/4 have had benefit. This new drug is considered worthy of further trial.
Clinical outcomes of patients with acute lymphoblastic leukemia receiving the hyper-CVAD regimen and assessment of the risk of hepatitis flares due to hepatitis B virus reactivation after chemotherapy. [2022]Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) has become a popular regimen for adults with acute lymphoblastic leukemia (ALL). We assessed the efficacy and tolerability of hyper-CVAD in the treatment of adult ALL.
Which steroids should we choose for the treatment of adult acute lymphoblastic leukemia? [2019]Corticosteroids are essential and one of the mainstays in the treatment of acute lymphoblastic leukemia (ALL). In vitro assays show that dexamethasone(DXM) is five to six times more cytotoxic to leukemic lymphoblasts than prednisolone (PDN) [1], and the use of DXM as an alternative drug for PDN is an important issue in the treatment of childhood ALL. The current randomized comparisons in childhood ALL indicated a statistically significant and clinically important decrease in rate of isolated central nervous system (CNS) relapses and an increase in event-free survival (EFS) with DXM. However, the data were limited in adult ALL. Recently, Labar et al. [2] reported their first investigation in comparison of the antileukemic activity and toxicity between DXM and PDN for adult patients with ALL and lymphoblastic lymphoma (LBL) through a randomized clinical trial (the ALL-4 trial of the EORTC Leukemia Group), and the author concluded that DXM as a steroid therapy for adult patients with ALL/LBL did not show any benefit compared with PDN, which did not support the experience from several other pediatric studies. In Labar’s observation, about 70% of adult patients were high risk (HR) ALL. Most of the patients in pediatric trials were standard risk (SR) ALL. In our study, we also evaluate the role of DXM compared with PDN during induction or subsequent phases of therapy in adult ALL with emphasis on SR group.
HRQOL implications of treatment with dexamethasone for children with acute lymphoblastic leukemia (ALL). [2016]Dexamethasone is increasingly used as the steroid of choice in trials for standard risk children with acute lymphoblastic leukemia (ALL). Improvements in event-free survival (EFS) have been attributed to lower CNS relapse rates, However, there are concerns that dexamethasone may be more toxic than previous conventional therapy with prednisone. Such toxicity raises questions about the implications for child neuropsychological function and HRQOL. Patients participating in the UK ALL 99/01 trial were randomized to receive dexamethasone or prednisone as their steroid in induction and maintenance chemotherapy. We compared the HRQOL and behavior in children randomized to receive both these agents.
Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. [2022]Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0.0007). Event-free survival was significantly improved with dexamethasone (84.2% vs. 75.6% at 5 years; P = 0.01), with no evidence of differing effects in any subgroup of patients. The use of 6.5 mg/m(2) dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.
Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. [2021]Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone (6 mg/m(2)/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m(2)/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system-directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7% +/- 0.8%, compared with 7.1% +/- 1.1% for prednisone (P =.01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% +/- 2% for dexamethasone and 77% +/- 2% for prednisone (P =.002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.