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Relapsed or Refractory Acute Myeloid LeukemiaPhase 1NCT04666649

Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)

A Phase 1 study testing Venetoclax and pegcrisantaspase in people with Relapsed or Refractory Acute Myeloid Leukemia, run by University of Maryland, Baltimore at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Evaluate the safety and tolerability of pegcrisantaspase in combination with venetoclax (Ven-PegC) and estimate the maximum tolerated doses and/or biologically active doses of Ven-PegC in patients with relapsed or refractory acute myeloid leukemia (R/R AML) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax and pegcrisantaspase
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
10 Mar 2021to 23 May 2025
Phase
Phase 1
Are there results?
None posted in the registry

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

  • A histologically or pathologically confirmed diagnosis of AML based on 2016 WHO classification. Patients with Complex Karyotype AML (CK-AML) and TP53-mutated AML are eligible for this study.
  • AML has relapsed after or is refractory to, first-line therapy, with a maximum of three prior lines of therapy. Patients whose AML has FLT3 or IDH1/IDH2 mutations should have received at least one available FLT3 or IDH1/IDH2 inhibitors
  • Age 18 years and older
  • ECOG performance status ≤ 2
  • Patients who have undergone allo-HSCT are eligible if they are ≥ 30 days post stem cell infusion, have no evidence of graft versus hose disease ( GVHD ) > Grade 1, and are ≥ 10 days off all immunosuppressive therapy
  • Previous cytotoxic chemotherapy must have been completed at least 10 days prior to day 1 of treatment on the study and all AEs (excluding alopecia, acne, rash) due to agents administered earlier should have recovered to < Grade 1. Patients with hematologic malignancies are expected to have hematologic abnormalities at study entry. These abnormalities which are thought to be primarily related to the underlying leukemia, are not considered to be toxicities (AE) and do not need to resolve to < Grade 1
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  • All biologic agents including hematopoietic growth factors must have been stopped at least 1 week prior to day 1 of treatment on the study
  • Patients must have adequate organ function as defined below:
  • Direct bilirubin ≤2X the institutional upper limit of normal (ULN) (except in patients with leukemic infiltration of the liver)
  • AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of the liver)
  • Alkaline phosphatase ≤5X ULN
  • Creatinine Clearance (CrCl) ≥ 45 mL/min (except in patients with evidence of tumor lysis syndrome)
  • Patients with a history of CNS leukemia must be stable with clear CSF for > 2 months prior to day 1 of treatment (patient can receive intrathecal maintenance chemotherapy)
  • Female patients of childbearing potential must have a negative pregnancy test <1 week prior to enrollment. Female patients of childbearing potential who are sexually active and male patients who are sexually active and have female partners of childbearing potential must agree to use highly effective method of contraception with their partners during exposure to study drugs and for 30 days after the last dose of study drugs.
  • Ability to understand and willingness to sign a written informed consent document.

Who cannot join

  • Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy
  • Patients with acute promyelocytic leukemia (APL) confirmed with t(15;17) (i.e. FAB subtype M3 and M3 variant)
  • Prior treatment with any asparaginase product. Patients who received ≤12 weeks of a BCL-2 inhibitor including venetoclax are eligible.
  • Absolute peripheral blast > 100,000/μL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The decision to start hydroxyurea during this time is at the discretion of the treating physician.
  • Patients with the following clinical histories are excluded:
  • severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis is defined by lipase elevation >5X ULN and with signs or symptoms
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  • unprovoked deep venous thrombosis (DVT)
  • pulmonary emboli
  • hemorrhagic or thromboembolic stroke
  • other malignancies requiring systemic chemotherapy, immunotherapy or targeted therapy in the last three months
  • Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements
  • Pregnant women and female patients who are lactating and do not agree to stop breast- feeding.
  • Uncontrolled active seizure
  • Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

Other trials in United States

About this study

Official title: Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Evaluate the safety and tolerability of pegcrisantaspase in combination with venetoclax (Ven-PegC) and estimate the maximum tolerated doses and/or biologically active doses of Ven-PegC in patients with relapsed or refractory acute myeloid leukemia (R/R AML)

Read the detailed description

This research study is a non-randomized, open-label Phase Ib clinical trial evaluating venetoclax (Ven) administered orally daily in combination with pegcrisantaspase (PegC) administered IV biweekly, as part of a 28-day treatment cycle in adult subjects with relapsed or refractory acute myeloid leukemia (R/R AML).

The trial will consist of dose escalation to evaluate the safety and tolerability of Ven-PegC and estimate the maximum tolerated doses (MTDs) and/or biologically active doses (e.g. recommended phase 2 doses [RP2Ds]) of Ven-PegC in patients with R/R AML

Venetoclax is an FDA (the U.S. Food and Drug Administration) approved drug, but this combination ( Ven-PegC) has not been approved by the FDA.

Being tested
Venetoclax and pegcrisantaspase
Keywords
Pegcrisantaspase, Venetoclax, Relapsed or refractory acute myeloid leukemia (R/R AML), Ven-PegC, Maximum tolerated doses, Recommended phase 2 doses, Incidence of regimen limiting toxicities, Incidence of treatment-emergent adverse events
Medical subject headings
Recurrence, Leukemia, Myeloid, Acute

What participants receive

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

  • Venetoclax and pegcrisantaspaseDrug

    Therapeutic

Study groups in NCT04666649
Study groupRoleWhat they receive
Cohort 400mg of Venetoclax, 500 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 500 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)
Receives: Drug: Venetoclax and pegcrisantaspase
Cohort 400mg of Venetoclax, 750 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 750 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)
Receives: Drug: Venetoclax and pegcrisantaspase
Cohort 400mg of Venetoclax, 1000 IU/m² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle)
Receives: Drug: Venetoclax and pegcrisantaspase
Cohort 600mg Venetoclax, 1000 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 600mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m ² of Pegcrisantaspase in an IV every 14 days ( Per cycle)
Receives: Drug: Venetoclax and pegcrisantaspase

What is being measured

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

  1. Incidence of regimen limiting toxicities (RLTs)

    The period for determination of RLT will be from the first day of treatment until 30 days after receiving the first dose of Ven-PegC.

    Measured: One year (after 12 cycle's treatment)

  2. Incidence of treatment-emergent adverse events (TEAE)

    The period for determination of TEAE will be from the first day of treatment until 30 days after receiving the first dose of Ven-PegC.

    Measured: One year (after 12 cycle's treatment)

Secondary outcomes (8)

  1. The rate of CR

    Complete Remission rate

    Measured: One year (after 12 cycle's treatment)

  2. The rate of composite complete remission (CR+CRh+CRi+CRp)

    The rate of Complete Remission rate, Complete Remission with Partial hematological recovery, Complete Remission with incomplete hematological recovery and Complete Remission with incomplete platelet recovery.

    Measured: One year (after 12 cycle's treatment)

  3. Event-free Survival (EFS)

    Event-free Survival (EFS)

    Measured: One year (after 12 cycle's treatment)

  4. Overall Survival (OS)

    Overall Survival (OS)

    Measured: One year (after 12 cycle's treatment)

  5. The rate of conversion from transfusion dependence to transfusion independence

    The rate of conversion from transfusion dependence to transfusion independence

    Measured: One year (after 12 cycle's treatment)

  6. The rate of proceeding to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after administration of Ven-PegC

    The rate of proceeding to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after administration of Ven-PegC

    Measured: One year (after 12 cycle's treatment)

  7. Achievement of MRD <0.02% within 2 cycles of treatment with Ven-PegC

    Achievement of Minimal Residual Disease <0.02% within 2 cycles of treatment with Ven-PegC

    Measured: Two months

  8. Overall incidence and severity of AEs

    Overall incidence and severity of Adverse Events

    Measured: One year (after 12 cycle's treatment)

Timeline

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

  1. First posted14 Dec 2020
  2. Study start10 Mar 2021
  3. Primary completion1 Sep 2024
  4. Study completion23 May 2025

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
1. Cohort1: The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 500 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle) 2. Cohort 2: The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 750 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle) 3. Cohort 3: The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle) 4. Cohort 4: The subject will take 600mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04666649
Sponsor's protocol ID
2087GCCC ; HP-00093729
Status last verified
Oct 2025
First submitted
7 Dec 2020
Last updated
7 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bade NA, Lu C, Patzke CL, Baer MR, Duong VH, Law JY, Lee ST, Sausville EA, Zimrin AB, Duffy AP, Lawson J, Emadi A. Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management. J Oncol Pharm Pract. 2020 Jan;26(1):74-92. doi: 10.1177/1078155219838316. Epub 2019 Mar 27.

    PubMed 30917738

  • American Cancer Society. Key Statistics for AML. 2020.

  • Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019 Sep 18;12(1):100. doi: 10.1186/s13045-019-0774-x.

    PubMed 31533852

  • Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544.

    PubMed 19776406

  • FDA. Vyxeos (daunorubicin and cytarabine) liposome Label. US Food and Drug Administration 2017:https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf.

  • Bose P, Vachhani P, Cortes JE. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options Oncol. 2017 Mar;18(3):17. doi: 10.1007/s11864-017-0456-2.

    PubMed 28286924

  • Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000 Dec 15;96(13):4075-83.

    PubMed 11110676

  • Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD; Cancer and Leukemia Group B (CALGB 8461). Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002 Dec 15;100(13):4325-36. doi: 10.1182/blood-2002-03-0772. Epub 2002 Aug 1.

    PubMed 12393746

  • Ciurea SO, Labopin M, Socie G, Volin L, Passweg J, Chevallier P, Beelen D, Milpied N, Blaise D, Cornelissen JJ, Fegueux N, Polge E, Kongtim P, Rondon G, Esteve J, Mohty M, Savani BN, Champlin RE, Nagler A. Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center. Cancer. 2018 May 15;124(10):2134-2141. doi: 10.1002/cncr.31311. Epub 2018 Feb 22.

    PubMed 29469961

  • Schoch C, Kern W, Kohlmann A, Hiddemann W, Schnittger S, Haferlach T. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosomes Cancer. 2005 Jul;43(3):227-38. doi: 10.1002/gcc.20193.

    PubMed 15846790

  • Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS. Acute Myeloid Leukemia: The Good, the Bad, and the Ugly. Am Soc Clin Oncol Educ Book. 2018 May 23;38:555-573. doi: 10.1200/EDBK_199519.

    PubMed 30231330

  • Grzmil M, Hemmings BA. Translation regulation as a therapeutic target in cancer. Cancer Res. 2012 Aug 15;72(16):3891-900. doi: 10.1158/0008-5472.CAN-12-0026. Epub 2012 Jul 31.

    PubMed 22850420

  • Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6.

    PubMed 23291630

  • FDA. Venetoclax (Venclexta). Food and Drug Administration 2018:https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf

  • DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.

    PubMed 30361262

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax and pegcrisantaspase in people with Relapsed or Refractory Acute Myeloid Leukemia, run by University of Maryland, Baltimore 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 15 inclusion and 15 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: finished, as of the sponsor's last update on 7 Oct 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of regimen limiting toxicities (RLTs) (time frame: One year (after 12 cycle's treatment)). The study lists 2 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 NCT04666649, which also lists 56 linked publications.

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 7 Oct 2025.

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