AzTrials
AzTrials

Hematopoietic and Lymphoid Cell NeoplasmPhase 1/2NCT04752163

DS-1594b With or Without Azacitidine, Venetoclax, or Mini-HCVD for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

A Phase 1/2 study testing DS-1594b, Azacitidine and Cyclophosphamide in people with Hematopoietic and Lymphoid Cell Neoplasm and Recurrent Acute Lymphoblastic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the effect of DS-1594b with or without azacitidine, venetoclax, or mini-HCVD in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has come back (recurrent) or not responded to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DS-1594b, Azacitidine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
25 Mar 2021to 8 Nov 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of written (signed) informed consent form (ICF) by the subject or legal guardian prior to the performance of any study-specific procedures, according to International Council on Harmonisation (ICH) and local regulatory requirements. Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible toxicities) and must sign and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF)(including Health Insurance Portability and Accountability Act authorization [HIPAA], if applicable) before performance of any study-specific procedures or examinations
  • Subjects must be willing and able to comply with the protocol
  • Subjects with AML or ALL, diagnosed according to the 2016 criteria by the World Health Organization (WHO) who are refractory or relapsed (any salvage) with no available therapies or not candidates for available therapies. For subjects with prior MDS or chronic myelomonocytic leukemia (CMML) or MPN who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML except for MDS or CMML treated with HMAs. Subjects with MDS or CMML treated with HMA therapies who progress to AML and have no available therapies or are not candidates for available therapies, will be eligible at the time of progression to AML. In Phase 1: all R/R AML or R/R ALL subjects irrespective of mutations will be eligible. In Phase 2 Cohort A only R/R AML with MLLr will be eligible. In Phase 2 Cohort B only R/R AML with NPM1m will be eligible. In Phase 2 Cohorts C and D: Only R/R AML or R/R ALL subjects with an MLLr or NPM1m will be eligible
  • Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is permitted
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
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  • Total bilirubin =< 1.5 times upper limit of normal (x ULN)
  • Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN (aspartate aminotransferase or alanine aminotransferase =< 5.0 x ULN if deemed related to leukemia by the treating physician)
  • Creatinine clearance >= 50 mL/min as calculated using the modified Cockcroft-Gault equation
  • Serum electrolytes within the institution's normal limits: potassium, calcium (total calcium, calcium corrected for serum albumin in case of hypoalbuminemia or ionized calcium) and magnesium. If outside of the institution's normal range, subject will be eligible when electrolytes are corrected
  • In the absence of rapidly progressive disease, the interval from prior treatment to the time of initiation of protocol therapy will be at least 14 days for prior anti-leukemic therapy with the exception of hydroxyurea as noted below OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is shorter. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document. Since the effect of therapy may be delayed, use of hydroxyurea for subjects with rapidly proliferative disease is allowed before the start of study therapy and on study and hydroxyurea will not require a washout
  • Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted. Subjects with a known history of CNS disease or leukemic brain metastasis must have been treated locally, have at least 3 consecutive lumbar punctures (LPs) with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable)
  • Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
  • Women of childbearing potential must agree to use an adequate method of contraception during the study and until 4 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include:
  • Total abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
  • Combination of any of the two following (a+b or a+c or b+c)
  • a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
  • b. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • In case of use of oral contraception, women should have been stable on the same pill before taking study treatment.
  • Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential

Who cannot join

  • Subjects with a known allergy, hypersensitivity, or contraindication to the protocol therapies or any of their components to be used in the arm the subject is to be enrolled on
  • Uncontrolled or significant cardiovascular disease, including any of the following:
  • Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;
  • Corrected QT interval Fridericia's Correction Formula (QTcF) interval > 450 msec;
  • Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
  • Systolic blood pressure >=180 mmHg or diastolic blood pressure >=110 mmHg;
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  • History of clinically relevant ventricular arrhythmias within 6 months prior to screening (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
  • History of second (Mobitz II) or third-degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
  • History of uncontrolled angina pectoris, unstable angina or myocardial infarction, coronary artery bypass graft (CABG), cerebrovascular accident (CVA), transient ischemia attack (TIA), symptomatic pulmonary emboli within 6 months prior to screening;
  • New York Heart Association Class 3 or 4 heart failure;
  • Left ventricular ejection fraction (LVEF) =< 50 or less than the institutional lower limit of normal;
  • Complete left bundle branch block (right bundle branch block is permitted, but requires manual reading of the QTc interval);
  • Active cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 (eg, atrial fibrillation)
  • Persisting toxicity related to prior therapy of grade > 1 NCI-CTCAE v 5.0; however, alopecia and sensory neuropathy grade 2 or lower is acceptable
  • Underwent HSCT within 90 days of the first dose of protocol therapy, or subjects with clinically significant (grade 2 or greater) graft-versus-host disease (GVHD) (the use of topical steroids for ongoing cutaneous GVHD is permitted)
  • Subjects with symptomatic CNS leukemia or subjects with poorly controlled CNS leukemia
  • Active and uncontrolled disease (active infection requiring systemic therapy, fever likely secondary to infection within prior 48 hours, uncontrolled hypertension despite adequate medical therapy as judged by the treating physician)
  • Active (uncontrolled, metastatic) other malignancies
  • Major surgery within 28 days prior to the first dose of protocol therapy
  • Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (test at screening only if required by local regulations)
  • Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with active Hepatitis B or C infection at screening (positive HBV surface antigen or HCV ribonucleic acid [RNA] if anti-HCV antibody screening test positive)
  • Vaccination within 4 weeks of the first dose of study drug and while on trials is prohibited except for administration of inactivated vaccines
  • Subjects who are currently receiving treatment with medication that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of DS-1594b treatment:
  • Medications that may prolong QTc interval and have a known risk of inducing Torsades de Pointes unless it is vital for the care of the subjects
  • Strong inhibitors or inducers of CYP3A
  • CYP3A and CYP2C19 substrates with narrow therapeutic index
  • Subjects who consume grapefruit products, Seville oranges, or star fruit within 3 days prior to the first DS-1594b administration and until the last day of DS-1594b is completed
  • SUB-STUDIES: Subjects who are currently receiving moderate inhibitors or inducers of CYP3A who cannot discontinue at least one week prior to the start of DS-1594b treatment till the end of sub-study period
  • SUB-STUDIES: Subjects who are currently receiving proton pump inhibitors who cannot discontinue at least 2 days prior to the start of DS-1594b treatment till the end of sub-study period
  • Other severe acute or chronic medical conditions that is active and not well controlled including renal, skeletal muscle, adrenal insufficiency, colitis, inflammatory bowel disease, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
  • Subjects unwilling or unable to comply with the protocol, including:
  • Pregnant or breastfeeding women or women of childbearing potential who are unable to comply with appropriate contraception as outlined in or who plan to become pregnant while in the study or for at least 6-7 months after last administration of study treatment
  • Known alcohol or drug abuse within the last 1 year
  • In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability to use an acceptable contraceptive method for the entire study period and for at least 3 months after study completion
  • Acute promyelocytic leukemia (APL)
  • Uncontrolled or poorly controlled adrenal or pituitary disease (including adrenal insufficiency, Addison's disease, Cushing's disease)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: An Open-Label Phase 1/2 Multi-Arm Study of DS-1594b as a Single-Agent and in Combination With Azacitidine and Venetoclax or Mini-HCVD for the Treatment of Patients With Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)

This phase I/II trial studies the effect of DS-1594b with or without azacitidine, venetoclax, or mini-HCVD in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia that has come back (recurrent) or not responded to treatment (refractory). Chemotherapy drugs, such as azacitidine, venetoclax, and mini-HCVD, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. DS-1594b may inhibit specific protein bindings that cause blood cancer. Giving DS-1594b, azacitidine, and venetoclax, or mini-HCVD may work better in treating patients with acute myeloid leukemia or acute lymphoblastic leukemia.

Read the detailed description

OUTLINE: This is a phase I, dose-escalation study of DS-1594b followed by a phase II study.

PHASE I: Patients receive DS-1594b orally (PO) twice daily (BID) on days 1-28 in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are assigned to 1 of 4 cohorts.

COHORT A: Patients with MLLr receive DS-1594b PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients with NPM1m receive DS-1594b PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

COHORT C: Patients receive DS-1594b PO BID on days 1-28, venetoclax PO QD on days 1-28, and azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

COHORT D: Patients receive DS-1594b PO BID on days 1-28. For cycles 1, 3, 5, 7, patients also receive cyclophosphamide IV over 3 hours on days 1-3, mesna IV over 24 hours on days 1-3, vincristine IV on days 1 and 11, dexamethasone PO or IV on days 1-4 and 11-14, filgrastim SC on days 1-28, methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, and cytarabine IT on day 7 of cycles 1 and 3. For cycles 2, 4, 6, 8, patients also receive methotrexate IV over 24 hours on day 1, cytarabine BID IV over 3 hours on days 2 and 3, leucovorin IV or PO every 6 hours (Q6H) starting 12 hours after completion of methotrexate, filgrastim SC days 1-28, cytarabine IT on day 5-8 of cycles 2 and 4 and methotrexate IT on days 8-11 of cycles 2 and 4. Patients with CD20 expression may also receive rituximab IV on days 1 and 11 of cycles 1 and 3 and days 1 and 8 of cycles 2 and 4. Cycles repeat every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients may then receive DS-1594b PO BID on days 1-28, vincristine IV over 15 minutes on day 7 and prednisone PO BID on days 1-5. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 30 and 100.

Medical subject headings
Hematologic Neoplasms, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DS-1594bDrug

    Given DS-1594b PO

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given IV or SC

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IT

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO or IV

  • FilgrastimBiological

    Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

    Given SC

  • LeucovorinDrug

    Also called Folinic acid

    Given IV or PO

  • MesnaDrug

    Also called 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna

    Given IV

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IT

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

  • VincristineDrug

    Also called Leurocristine, VCR, Vincrystine

    Given IV

Study groups in NCT04752163
Study groupRoleWhat they receive
Cohort A and B (DS-1594b)ExperimentalPatients with MLLr or NPM1m receive DS-1594b PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: DS-1594b
Cohort C (DS-1594b, venetoclax, azacitidine)ExperimentalPatients receive DS-1594b PO BID on days 1-28, venetoclax PO QD on days 1-28, and azacitidine IV or SC on days 1-7. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: DS-1594b; Drug: Azacitidine; Drug: Venetoclax
Cohort D (DS-1594b, mini-HCVD)ExperimentalPatients receive DS-1594b PO BID on days 1-28. For additional information, see trial description.
Receives: Drug: DS-1594b; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Biological: Filgrastim; Drug: Leucovorin; Drug: Mesna; Drug: Methotrexate; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine
Phase I (DS-1594b) Cohort 1ExperimentalPatients receive DS-1594b PO BID on days 1-28 in the absence of disease progression or unacceptable toxicity. 70 mg twice daily.
Receives: Drug: DS-1594b
Phase I (DS-1594b) Cohort 2ExperimentalPatients receive DS-1594b PO BID on days 1-28 in the absence of disease progression or unacceptable toxicity. 50 mg twice daily.
Receives: Drug: DS-1594b
Phase I (DS-1594b) Cohort 3ExperimentalPatients receive DS-1594b PO BID on days 1-28 in the absence of disease progression or unacceptable toxicity. 20 mg daily.
Receives: Drug: DS-1594b
Phase I (DS-1594b) Cohort 4ExperimentalPatients receive DS-1594b PO BID on days 1-28 in the absence of disease progression or unacceptable toxicity. 50 mg daily.
Receives: Drug: DS-1594b
Phase I (DS-1594b) Cohort 5ExperimentalPatients receive DS-1594b PO BID on days 1-28 in the absence of disease progression or unacceptable toxicity. 100 mg daily.
Receives: Drug: DS-1594b

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) (Phase I)

    The highest dose of DS-1594b treatment that does not cause unacceptable side effects.

    Measured: Day 28

  2. Recommended Phase 2 Dose (RP2D) (Phase I)

    This will be selected based upon the cumulative safety, efficacy and PK data at the end of the Phase 1 portion when the maximum tolerated dose is found. This will be One dose level below the RP2D of DS-1594b from Phase 1.

    Measured: Day 28

  3. Number of Participants With Complete Remission (CR) and Complete Remission With Partial Hematologic Recover (CRh)With DS-1594b Monotherapy in (Phase II, Cohort A)

    AML Participants: (CR) is No circulating blasts, Neutrophils > 1.0 x 10 ^ 9/L OR Platelet Count > 100 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods, No extramedullary leukemia. (CRh) is defined No circulating blasts, Neutrophils >/= 0.5 x 10 ^ 9/L, Platelet Count >/= 50 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods. ALL Participants: (CR) is No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count > 1.0 x 10 ^ 9/L, platelet count > 100 x 10 ^ 9/L, No recurrence for 4 weeks. (CRh) No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count >/= 0.5 x 10 ^ 9/L, >/= 50 x 10 ^ 9/L, No recurrence for 4 weeks.

    Measured: 3 months

  4. Number of Participants Who Achieved CR/CRh With DS-1594b Monotherapy in R/R AML With Nucleophosmin 1 Mutation (NPM1m) (Phase II, Cohort B)

    AML Participants: (CR) is No circulating blasts, Neutrophils > 1.0 x 10 ^ 9/L OR Platelet Count > 100 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods, No extramedullary leukemia. (CRh) is defined No circulating blasts, Neutrophils >/= 0.5 x 10 ^ 9/L, Platelet Count >/= 50 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods.

    Measured: 3 months

  5. Number of Participants Who Achieved CR+CRh With DS1594b in Combination With Azacitidine and Venetoclax in R/R MLLr or R/R NPM1m AML (Phase II, Cohort C)

    AML Participants: (CR) is No circulating blasts, Neutrophils > 1.0 x 10 ^ 9/L OR Platelet Count > 100 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods, No extramedullary leukemia. (CRh) is defined No circulating blasts, Neutrophils >/= 0.5 x 10 ^ 9/L, Platelet Count >/= 50 x 10 ^ 9/L, Bone marrow aspirate and biopsy <5% blasts, No Auer rods.

    Measured: 3 months

  6. Number of Participants Who Achieved CR+CRh With DS1594b in Combination With Mini-HCVD in R/R ALL With MLLr (Phase II, Cohort D)

    ALL Participants: (CR) is No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count > 1.0 x 10 ^ 9/L, platelet count > 100 x 10 ^ 9/L, No recurrence for 4 weeks. (CRh) No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count >/= 0.5 x 10 ^ 9/L, >/= 50 x 10 ^ 9/L, No recurrence for 4 weeks.

    Measured: 3 months

  7. CR+ Complete Remission With Incomplete Hematologic Recovery (CRi) Rate of DS-1594b in Combination With Mini-HCVD in R/R ALL With MLLr (Phase II Cohort D)

    ALL Participants: (CR) is No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count > 1.0 x 10 ^ 9/L, platelet count > 100 x 10 ^ 9/L, No recurrence for 4 weeks. (CRh) No circulating lymphoblast or extramedullary disease, No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement. Trilineage hematopoiesis (TLH) and <5% blasts, Neutrophil count >/= 0.5 x 10 ^ 9/L, >/= 50 x 10 ^ 9/L, No recurrence for 4 weeks.

    Measured: 3 months

Secondary outcomes (13)

  1. Composite CR (CRc) Rate

    Defined as CR + complete remission with incomplete blood count recovery (CRi), morphologic leukemia free survival (MLFS), partial remission (PR), and overall response rate of subjects with R/R AML and R/R ALL treated on single-agent or combinations of DS-1594b.

    Measured: Up to 2 years

  2. Participants With Morphologic Leukemia-free State (MLFS)

    AML Participants: Bone marrow < 5% myeloblasts, no auer rods, no extramedullary leukemia, neutrophil or platelet recovery is not required.

    Measured: Up to 2 years

  3. Participants With a Partial Response (PR)

    Partial remission (PR), Neutrophil count: >1.0 x109/L, Platelet count >100 x109/L, ≥ 50 % reduction in bone marrow blast from pretreatment baseline, but still ≥ 5%.

    Measured: Up to 2 years

  4. Number of Participants With a Response

    Defined as CR + CRi + MLFS + PR. Complete remission (CR), Peripheral blood counts: No circulating blasts, Neutrophil count: >1.0 x109/L, Platelet count >100 x109/L, Bone marrow aspirate and biopsy: < 5% blasts, No Auer rods, No extramedullary leukemia. CRi is the same as CR except Neutrophil count: <1.0 x109/L, OR Platelet count: <100 x109/L. MLFS is Bone marrow < 5% myeloblasts, No Auer rods, No extramedullary leukemia, Neutrophil or platelet recovery is not required. PR is Neutrophil count: >1.0 x109/L, Platelet count >100 x109/L, >/= 50 % reduction in bone marrow blast from pretreatment baseline, but still >/= 5%

    Measured: Up to 2 years

  5. Duration of Response

    Response date to loss of response or last follow up.

    Measured: Up to 2 years

  6. Time to First Response and Time to Best Response

    First response date to best response date.

    Measured: Up to 2 years

  7. Rate of Durable Transfusion Independence (TI)

    TI is defined as the absence of red blood cell and platelet transfusions for a consecutive 56-day period during continued treatment.

    Measured: Up to 2 years

  8. Event-free Survival

    Time from date of treatment start until the date of failure or death from any cause.

    Measured: Up to the date of failure or death from any cause, approximately 2 years, 7 months

  9. Overall Survival

    Estimated using the Kaplan-Meier method.From the date of the treatment start to the date of death or to the date of last follow-up if patients are alive at the time of data collection

    Measured: Up to the date of death or last follow-up, approximately 2 years, 7 months

  10. Mortality Rate

    Number of deaths to occur within 4 weeks from start of therapy to 4 weeks into therapy.

    Measured: 4 weeks

  11. Mortality Rate

    Number of deaths to occur within 8 weeks from start of therapy to 8 weeks into therapy.

    Measured: 8 weeks

  12. Number of Subjects Able to Proceed to Hematopoietic Stem Cell Transplantation (HSCT) Without Additional AML Therapy

    Measured: Up to 2 years

  13. Median Duration to HSCT From the Initiation of Single-agent or Combinations of DS-1594b in Subjects With RR AML and R/R ALL

    Calculated time to HSCR for participants who went on to HSCT.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2021
  2. Study start25 Mar 2021
  3. Primary completion8 Nov 2023
  4. Study completion8 Nov 2023

Why it stopped: supporting/funding source decided to de-prioritize and stop development of DS-1594

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04752163
Sponsor's protocol ID
2020-0946
Other IDs
NCI-2021-00603, 2020-0946
Status last verified
May 2025
First submitted
3 Feb 2021
Last updated
23 May 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Numata M, Haginoya N, Shiroishi M, Hirata T, Sato-Otsubo A, Yoshikawa K, Takata Y, Nagase R, Kashimoto Y, Suzuki M, Schulte N, Polier G, Kurimoto A, Tomoe Y, Toyota A, Yoneyama T, Imai E, Watanabe K, Hamada T, Kanada R, Watanabe J, Kagoshima Y, Tokumaru E, Murata K, Baba T, Shinozaki T, Ohtsuka M, Goto K, Karibe T, Deguchi T, Gocho Y, Yoshida M, Tomizawa D, Kato M, Tsutsumi S, Kitagawa M, Abe Y. A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1. Cancer Cell Int. 2023 Feb 25;23(1):36. doi: 10.1186/s12935-023-02877-y.

    PubMed 36841758

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DS-1594b, Azacitidine and Cyclophosphamide in people with Hematopoietic and Lymphoid Cell Neoplasm and Recurrent Acute Lymphoblastic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (Phase I) (time frame: Day 28). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04752163, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.

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