DSP-5336 for Leukemia
Recruiting in Palo Alto (17 mi)
+46 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Sumitomo Pharma America, Inc.
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called DSP 5336 to help treat adults with certain types of blood cancer that have come back or didn't respond to previous treatments. The study will first find the best amount to give and then check how safe and helpful it is.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you must stop all current medications. However, you cannot take systemic calcineurin inhibitors within 4 weeks before the trial, certain antifungals like ketoconazole and itraconazole, immunotherapy within 42 days, other investigational treatments within 4 weeks, or antineoplastic agents within 14 days before the trial. If you're on excluded antifungals, you can switch to a permitted one 7 days before starting the trial. Please consult with the trial team for specific guidance on your medications.
What data supports the idea that DSP-5336 for Leukemia is an effective drug?
The available research does not provide any specific data on DSP-5336 for Leukemia. Instead, it discusses other treatments for related conditions like myelodysplastic syndromes and acute myeloid leukemia. For example, 5-azacytidine has shown effectiveness in some patients with these conditions, achieving complete remission in certain cases. However, without specific data on DSP-5336, we cannot conclude its effectiveness for Leukemia based on the provided information.
12345What safety data is available for DSP-5336 in leukemia treatment?
The provided research does not contain any safety data specifically related to DSP-5336 or its other names for leukemia treatment. The studies focus on different antiemetic drugs and their effects, none of which are related to DSP-5336.
678910Eligibility Criteria
This trial is for adults with relapsed or refractory Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL), who have failed standard treatments. Phase 1 includes those with certain genetic abnormalities, while Phase 2 requires a confirmed diagnosis of AML with specific mutations. Participants must be in good physical condition, not pregnant, and willing to use effective contraception.Inclusion Criteria
Alanine aminotransferase (ALT) ≤3.0 times ULN
I have AML that didn't respond to treatment and have specific genetic changes.
Aspartate aminotransferase (AST) ≤3.0 times ULN
+12 more
Exclusion Criteria
My leukemia is causing severe or life-threatening issues.
For sites in Japan only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs) antibody test should be performed if HBsAg is negative. If HBc antibody or HBs antibody test is positive, HBV DNA quantification test should be performed to confirm that HBV DNA is negative.
I haven't taken cancer drugs, except for hormone therapy or hydroxyurea, in the last 14 days.
+24 more
Participant Groups
The study tests DSP-5336, a new drug for patients whose leukemia has returned after treatment or hasn't responded to previous therapies. It's conducted in two parts: first determining the right dose and then expanding that dose to more patients with particular genetic markers.
4Treatment groups
Experimental Treatment
Group I: Phase 2 Arm B: AML with NPM1c mutationsExperimental Treatment1 Intervention
Patients with R/R AML w/ NPM1c mutations
Group II: Phase 2 Arm A AML with MLL (KMT2A) gene rearrangementsExperimental Treatment1 Intervention
Patients with R/R AML w/MLL (KMT2A) gene rearrangements
Group III: Phase 1 Arm B with AntifungalsExperimental Treatment1 Intervention
Patients receiving anti-fungals that are moderate to strong cytochrome CYP3A4/5 inhibitors (i.e. Posaconazole, voriconazole, fluconazole, or isavuconazonium (prodrug of isavuconazole).
Group IV: Phase 1 Arm A without AntifungalsExperimental Treatment1 Intervention
Patients not taking antifungals within 7 days of study entry
DSP-5336 is already approved in United States for the following indications:
🇺🇸 Approved in United States as DSP-5336 for:
- Relapsed/refractory acute myeloid leukemia (AML) with KMT2A rearrangement or NPM1 mutation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke UniversityDurham, NC
Sibley Memorial HospitalBaltimore, MD
Johns Hopkins Main CenterBaltimore, MD
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Sumitomo Pharma America, Inc.Lead Sponsor
Sumitomo Dainippon Pharma Oncology, IncLead Sponsor
Sumitomo Pharma Oncology, Inc.Lead Sponsor
References
Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis. [2022]Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.
CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. [2019]Thrombocytopenia is among the strongest predictors of decreased survival for patients with myelodysplastic syndromes (MDS) across all prognostic risk groups. The safety and efficacy of CC-486 (oral azacitidine) was investigated in early-phase studies; we assessed clinical outcomes among subgroups of MDS patients from these studies, defined by presence or lack of pretreatment thrombocytopenia (≤75 × 109/L platelet count). Patients received CC-486 300 mg once-daily for 14 or 21 days of repeated 28-day cycles. Overall, 81 patients with MDS, median age 72 years, comprised the Low Platelets (n = 45) and High Platelets (n = 36) cohorts. Pretreatment median platelet counts were 34 × 109/L and 198 × 109/L, respectively. Grade 3-4 bleeding events occurred in 2 patients in the Low Platelets and 1 patient in the High Platelets groups; events resolved without sequelae. Treatment-related mortality was reported for 7 patients, 5 of whom had pretreatment platelet values <25 × 109/L. Overall response rates were 38% and 46% in the Low Platelets and High Platelets groups, respectively. Five thrombocytopenic patients attained complete remission and 9 attained platelet hematologic improvement. In both cohorts, platelet counts dropped during the first CC-486 treatment cycle, then increased thereafter. Extended CC-486 dosing was generally well tolerated and induced hematologic responses in these patients regardless of pretreatment thrombocytopenia.
Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. [2023]To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia.
Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. [2013]The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)
Induction of complete remission in a patient with acute myeloid leukemia refractory to high-dose chemotherapy through treatment with 5-azacytidine. [2013]For patients with acute myeloid leukemia refractory to intensive chemotherapy prognosis is very poor and treatment options are limited. 5-Azacytidine, a demethylating drug, is effective in the treatment of myelodysplastic syndromes when administered at a low-dose, subcutaneously. We report a case of a patient with AML refractory to induction chemotherapy as well as to two high-dose salvage regimens. The patient achieved CR through monotherapy with low-dose azacytidine.
Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin. [2019]High dose metoclopramide and adjuvant drugs, such as corticosteroids, benzodiazepines, and drugs with antidopaminergic, anticholinergic, or antihistaminic effects, are the most widely used antiemetics in cancer patients receiving chemotherapy, particularly cis-dichloro-diammine platinum II (cisplatin). The purpose of our prospective randomized study was to investigate the possible antiemetic efficacy of diphenhydramine as an adjuvant antiemetic drug when combined with metoclopramide (MCP). A total of 91 patients were assigned to either group A (N = 44) who received only MCP and group B (N = 47) who received the combination of MCP and diphenhydramine. All patients received cisplatin-based combination chemotherapy for the first time and were evaluated only once in order to exclude the effects of anticipatory nausea and vomiting. There were no statistically significant differences between the two groups except that patients treated with diphenhydramine presented more sedative effects and had more limited activity. Also diphenhydramine did not give absolute protection from the extrapyramidal side effects of MCP. Side effects of diphenhydramine were minimal and well tolerated. We conclude that diphenhydramine is not a useful adjuvant drug in the antiemetic therapy.
Dose-ranging evaluation of the substituted benzamide dazopride when used as an antiemetic in patients receiving anticancer chemotherapy. [2019]Dazopride, a substituted benzamide structurally related to metoclopramide, is a potent gastric prokinetic agent that prevents cisplatin-induced emesis in animals. Unlike metoclopramide, dazopride has no effect on dopamine receptors and therefore should not produce extrapyramidal side effects. In this dose-ranging trial, 23 patients with cancer receiving chemotherapy known to produce nausea and vomiting received three i.v. infusions of dazopride every 2 h beginning 30 min before the chemotherapy. Seven dose levels were explored ranging from 0.5 to 4.0 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, visual disturbances, and headaches. All side effects were transient and were not dose-related. Antiemetic effects were observed. Dazopride can be safely given on this schedule at doses of up to 4.0 mg/kg to patients receiving chemotherapy. On the basis of the results of this trial, further studies of this agent are warranted.
Antiemetic therapy in patients treated with high-dose cytosine arabinoside. [2018]The antiemetic efficacy of metoclopramide (MCP) was evaluated in 33 consecutive patients treated with high-dose cytosine arabinoside (HiDAC), greater than or equal to 3 g/m2, a highly emetogenic agent increasingly used in patients with hematologic malignancies for which no previous formal antiemetic trials have been reported. Administration of MCP in conjunction with prophylactic diphenhydramine resulted in major antiemetic responses (0-2 episodes of emesis in the 24 h after therapy) in 23 of 33 (70%) patients. The addition of lorazepam (LZP) to MCP resulted in major antiemetic response in 7 or 8 (88%) patients who failed to respond to MCP alone. Major side effects were extrapyramidal reactions (5%) and moderate diarrhea (18%). MCP alone or in conjunction with LZP is effective antiemetic therapy in patients treated with HiDAC.
Sulpiride versus metoclopramide in nononcologic patients with vomiting or nausea. [2019]Metoclopramide, a benzamide substitute, is used frequently as an antiemetic drug. Sulpiride, another benzamide substitute, was investigated and found to be safe and effective in a handful of studies involving only oncologic or other severely symptomatic patients. In this investigation the authors compared prospectively the antiemetic efficacy of sulpiride versus metoclopramide in a double-blind, randomized study involving 36 nononcologic patients with transient vomiting or nausea of various etiologies. Each group of 18 patients received oral metoclopramide or sulpiride (10 mg or 50 mg respectively) every 8 hours for a total of three doses each (24 hours of treatment). A 5-point score was used to evaluate symptomatic relief. Efficacy of the two drugs proved similar, and at the end of the study, 14 and 13 of 18 patients on sulpiride or metoclopramide respectively were asymptomatic. Only transient, minor side effects were reported in one patient in each group. The authors conclude that sulpiride is an effective and safe antiemetic drug that can be adopted legitimately in such cases as a first choice, or serve as an equipotent alternative to metoclopramide in patients sensitive to the latter.
Development and evaluation of 6-mercaptopurine and metoclopramide polypill formulation for oral administration: In-vitro and ex vivo studies. [2021]The present investigation was to develop a polypill of 6-mercaptopurine and metoclopramide. A polypill with delayed release granules of an anticancer and immediate release mucoadhesive tablet of antiemetic may result in the reduction of emesis caused by oral chemotherapy.
Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. [2023]The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid malignancies characterized by multilineage cytopenias, recurrent cytogenetic abnormalities, and risk of progression to acute myeloid leukemia (AML). AML, which can occur de novo as well as secondary to MDS, is characterized by malignant clones of myeloid lineage in the bone marrow and peripheral blood, with dissemination into tissues. The cytidine nucleoside analog and epigenetic modifier azacitidine is approved in the U.S. for the treatment of all French-American-British subtypes of MDS and in many countries for the treatment of AML with 20%-30% blasts and multilineage dysplasia according to the World Health Organization classification. Benefits of azacitidine treatment of patients with AML with >30% blasts have also been shown in a recent phase III trial. Oral administration of azacitidine may enhance patient convenience, eliminate injection-site reactions, allow for alternative dosing and scheduling, and enable long-term treatment. Phase I studies with oral azacitidine (CC-486) have shown biological activity, clinical responses, and tolerability in patients with MDS and AML. Extended dosing schedules of oral azacitidine (for 14 or 21 days of 28-day cycles) are currently under investigation as frontline therapy in patients with lower risk MDS, as maintenance therapy for patients with AML not eligible for stem cell transplant, and as maintenance therapy for patients with MDS or AML following stem cell transplant. This review presents clinical data supporting the use of injectable azacitidine in MDS and AML and examines the rationale for and results of the clinical development of oral azacitidine.
Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. [2022]Label="PURPOSE">Outcomes are poor in TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), even after allogeneic hematopoietic stem-cell transplant (HCT). Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator.
Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia. [2023]CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described.
Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. [2023]TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia.
CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. [2022]5-Azacytidine, a DNA methyl transferase inhibitor, is effective in patients with myelodysplastic syndromes (MDS). Whether responses to 5-Azacytidine are achieved by demethylation of key genes or by cytotoxicity is unclear. Of 34 patients with MDS or acute myeloid leukaemia (AML) treated with 5-Azacytidine, 7 achieved complete remissions (CR) (21%) and 6 achieved haematological improvement. All six had less than 5% bone marrow (BM) blasts at the time of haematological improvements (HI) (2 had pre-existing refractory anaemia (RA), 4 had refractory anaemia with excess blasts (RAEB)). A further patient with RAEB had blast reduction to less than 5% without HI. Five of the seven (71%) complete responders had chromosome 7 abnormalities. BM CR predicted longer overall survival (OS) (median 23 versus 9 months, P=0.015). Bisulphite genomic sequencing (BGS) of the CDKN2B (p15(INK4b)) promoter showed low level, heterogeneous pretreatment methylation (mean 12.2%) in 14/17 (82%) patients analysed. Lower baseline methylation occurred in responders (9.8% versus 16.2% in non-responders P=0.07). No response was seen in patients with >24% methylation, in whom p15(INK4b) mRNA was not expressed. 5-Azacytidine reduced CDKN2B methylation by mean 6.8% in 8/17 (47%) patients, but this did not correlate with response. At 75 mg/m(2), cell death (reduced BM cellularity (P=0.001) and increased apoptosis (P=0.02)) rather than demethylation of CDKN2B correlates with response. Patients with >24% methylation may benefit from alternative dosing or combination strategies.