DSP-5336 for Leukemia

Recruiting at 92 trial locations

Overseen By Tomoko Kuwabara

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sumitomo Pharma America, Inc.

Must not be taking: Calcineurin inhibitors, CYP3A4/5 inhibitors

Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

362 Participants Needed

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like systemic calcineurin inhibitors or specific antifungals close to starting the trial. It's best to discuss your current medications with the trial team.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug DSP-5336 for leukemia?

While there is no direct data on DSP-5336, similar treatments like 5-azacytidine have shown effectiveness in treating blood-related disorders such as myelodysplastic syndromes and acute myeloid leukemia, with some patients achieving complete remission. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

Is the drug DSP-5336 a promising treatment for leukemia?

The information provided does not mention DSP-5336, so we cannot determine if it is a promising treatment for leukemia based on the given data. ^{11 12 13 14 15}

Eligibility 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

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Determine the recommended Phase 2 dose (RP2D) based on the lowest dose of Enzomenib (DSP-5336) that provides the maximum biologic and clinical effect, or the MTD, whichever is lower

2 months

Phase 2: Dose Expansion

Further evaluate the safety and clinical activity of Enzomenib (DSP-5336) monotherapy in patients with relapsed/refractory AML who have MLLr or NPM1m, and relapsed/refractory ALL who have MLLr

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DSP-5336

Trial Overview 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.

Participant Groups

Group I: Phase 2 - Arm I Experimental Treatment 1 Intervention

R/R ALL with MLLr

Group II: Phase 2 - Arm H Experimental Treatment 1 Intervention

R/R AML with NPM1m

Group III: Phase 2 - Arm G Experimental Treatment 1 Intervention

R/R AML with MLLr

Group IV: Phase 1 - Arm F Experimental Treatment 2 Interventions

Patients with AML

Group V: Phase 1 - Arm E Experimental Treatment 3 Interventions

Patients with AML

Group VI: Phase 1 - Arm C Experimental Treatment 1 Intervention

Patients with MDS

Group VII: Phase 1 - Arm B Experimental Treatment 2 Interventions

Patients receiving antifungals that are moderate to strong cytochrome CYP3A4/5 inhibitors (i.e. posaconazole, voriconazole, or fluconazole).

Group VIII: Phase 1 - Arm A Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Sumitomo Pharma America, Inc.

Lead Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

Sumitomo Dainippon Pharma Oncology, Inc

Lead Sponsor

Trials

42

Recruited

6,800+

Sumitomo Pharma Oncology, Inc.

Lead Sponsor

Trials

45

Recruited

7,100+

Findings from Research

Eltrombopag and romiplostim significantly reduced the incidence of grade ≥3 bleeding events in patients with myelodysplastic syndromes (MDS), indicating their potential safety and efficacy in managing bleeding complications.

However, these treatments were associated with a lower overall response rate (ORR) in MDS, particularly in patients receiving eltrombopag or those with intermediate- or high-risk MDS, suggesting a need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis. Meng, F., Chen, X., Yu, S., et al.[2022]

In a study of 81 patients with myelodysplastic syndromes (MDS), CC-486 (oral azacitidine) was found to be generally safe and effective, with overall response rates of 38% in patients with low platelet counts and 46% in those with normal platelet counts.

Despite initial drops in platelet counts during treatment, CC-486 led to hematologic improvements in both groups, indicating its potential as a treatment option for MDS patients regardless of their pretreatment thrombocytopenia status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. Garcia-Manero, G., Scott, BL., Cogle, CR., et al.[2019]

In a pooled analysis of treatment-naïve patients with FLT3-mutant acute myeloid leukemia, the combination of venetoclax and azacitidine resulted in a significantly higher composite complete remission rate (67%) compared to azacitidine alone (36%), with a median overall survival of 12.5 months versus 8.6 months.

The treatment was found to be safe, with no unexpected toxicities reported, indicating that venetoclax + azacitidine is a promising option for older patients or those with comorbidities who are ineligible for intensive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. Konopleva, M., Thirman, MJ., Pratz, KW., et al.[2023]

In a study of 43 patients with refractory anemia and excess blasts, 5-azacytidine treatment resulted in a 49% response rate, with 12% achieving complete remission and 25% achieving partial remission, indicating its potential efficacy in treating myelodysplastic syndrome (MDS).

The treatment led to significant improvements in erythroid progenitor cell growth, correlating with increased hemoglobin levels and reduced need for blood transfusions, while side effects were generally mild to moderate, with myelosuppression occurring in only 33% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Silverman, LR., Holland, JF., Weinberg, RS., et al.[2013]

A patient with acute myeloid leukemia (AML) that did not respond to intensive chemotherapy achieved complete remission (CR) using low-dose 5-Azacytidine as a monotherapy.

This case suggests that low-dose 5-Azacytidine, a demethylating agent typically used for myelodysplastic syndromes, may be a promising treatment option for patients with refractory AML, where traditional treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of complete remission in a patient with acute myeloid leukemia refractory to high-dose chemotherapy through treatment with 5-azacytidine. Kuendgen, A., Gräf, T., Zohren, F., et al.[2013]

In a study of 91 cancer patients receiving cisplatin-based chemotherapy, the combination of metoclopramide and diphenhydramine did not show significant improvements in antiemetic efficacy compared to metoclopramide alone.

While diphenhydramine caused more sedation and limited activity in patients, its side effects were minimal and well tolerated, leading to the conclusion that it is not a beneficial adjuvant in antiemetic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin. Tsavaris, N., Zamanis, N., Zinelis, A., et al.[2019]

Dazopride, a gastric prokinetic agent, was tested in a dose-ranging trial with 23 cancer patients undergoing chemotherapy, showing effective prevention of nausea and vomiting without the extrapyramidal side effects associated with similar drugs like metoclopramide.

The treatment was well-tolerated at doses up to 4.0 mg/kg, with only mild and transient side effects such as sedation and dizziness, indicating its safety for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging evaluation of the substituted benzamide dazopride when used as an antiemetic in patients receiving anticancer chemotherapy. Grant, SC., Kris, MG., Gralla, RJ., et al.[2019]

In a study of 33 patients receiving high-dose cytosine arabinoside (HiDAC), metoclopramide (MCP) combined with diphenhydramine achieved a major antiemetic response in 70% of patients, significantly reducing vomiting episodes.

Adding lorazepam (LZP) to MCP improved the antiemetic response to 88% in patients who did not initially respond to MCP alone, indicating that MCP is an effective treatment for nausea and vomiting associated with HiDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic therapy in patients treated with high-dose cytosine arabinoside. Craig, JB., Powell, BL., White, DR., et al.[2018]

In a double-blind, randomized study of 36 nononcologic patients, sulpiride was found to be as effective as metoclopramide in relieving nausea and vomiting, with 14 patients on sulpiride and 13 on metoclopramide becoming asymptomatic after treatment.

Both drugs were well-tolerated, with only minor side effects reported, suggesting that sulpiride is a safe and effective alternative to metoclopramide for treating nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sulpiride versus metoclopramide in nononcologic patients with vomiting or nausea. Cohen, N., Alon, I., Almoznino-Sarfian, D., et al.[2019]

The study successfully developed a polypill combining 6-mercaptopurine and metoclopramide, which aims to reduce nausea caused by chemotherapy, with the polypill designed to release metoclopramide immediately before the delayed release of 6-mercaptopurine.

Formulation F7 of 6-mercaptopurine showed optimal drug release over 2 hours, while formulation M2 of metoclopramide demonstrated effective mucoadhesion lasting over 15 minutes, indicating potential for improved therapeutic outcomes in managing chemotherapy-induced emesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of 6-mercaptopurine and metoclopramide polypill formulation for oral administration: In-vitro and ex vivo studies. Chowdhary, R., Pai, RS., Singh, G.[2021]

Azacitidine is an approved treatment for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), showing benefits even in patients with higher blast counts, as demonstrated in recent phase III trials.

Oral azacitidine (CC-486) has shown promising biological activity and tolerability in early studies, potentially offering a more convenient treatment option for patients with MDS and AML, with ongoing investigations into extended dosing schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cogle, CR., Scott, BL., Boyd, T., et al.[2023]

In a phase II trial involving 55 patients with TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), maintenance therapy with eprenetapopt and azacitidine showed a median relapse-free survival (RFS) of 12.5 months and a 1-year RFS probability of 59.9%.

The treatment was well tolerated, with a median overall survival (OS) of 20.6 months and a 1-year OS probability of 78.8%, indicating promising outcomes for this high-risk patient group after hematopoietic stem-cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. Mishra, A., Tamari, R., DeZern, AE., et al.[2022]

CC-486, an oral formulation of azacitidine, showed a 40% overall response rate in patients with lower-risk myelodysplastic syndromes (MDS) and poor prognostic features, including significant improvements in hematologic conditions and sustained RBC transfusion independence in 47% of transfusion-dependent patients.

The ongoing phase 3 QUAZAR trial aims to further evaluate the efficacy and safety of CC-486 compared to placebo, focusing on achieving RBC transfusion independence for at least 84 days, which could potentially expand treatment options for patients with lower-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Garcia-Manero, G., Almeida, A., Giagounidis, A., et al.[2023]

In a phase 1 study involving 49 patients with TP53-mutated acute myeloid leukaemia, the combination of eprenetapopt and venetoclax with azacitidine showed promising efficacy, with 64% of patients achieving an overall response and 38% achieving a complete response.

The treatment demonstrated an acceptable safety profile, with no dose-limiting toxicities observed and manageable adverse events, suggesting it is a viable option for further evaluation in frontline therapy for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Garcia-Manero, G., Goldberg, AD., Winer, ES., et al.[2023]

In a study of 34 patients with myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML) treated with 5-Azacytidine, 21% achieved complete remissions, indicating its efficacy as a treatment option.

The response to 5-Azacytidine was more closely associated with cytotoxic effects, such as increased cell death and reduced bone marrow cellularity, rather than the demethylation of the CDKN2B gene, suggesting that higher doses or combination therapies may be needed for patients with high baseline methylation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. Raj, K., John, A., Ho, A., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Induction of complete remission in a patient with acute myeloid leukemia refractory to high-dose chemotherapy through treatment with 5-azacytidine. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Dose-ranging evaluation of the substituted benzamide dazopride when used as an antiemetic in patients receiving anticancer chemotherapy. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Antiemetic therapy in patients treated with high-dose cytosine arabinoside. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Sulpiride versus metoclopramide in nononcologic patients with vomiting or nausea. [2019]

10. India pubmed.ncbi.nlm.nih.gov

Development and evaluation of 6-mercaptopurine and metoclopramide polypill formulation for oral administration: In-vitro and ex vivo studies. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. [2022]

13. England pubmed.ncbi.nlm.nih.gov

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]

14. England pubmed.ncbi.nlm.nih.gov

Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. [2023]

15. England pubmed.ncbi.nlm.nih.gov

CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. [2022]