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Acute Myeloid LeukemiaPhase 2NCT06337331

Adding Venetoclax to the High-dose Chemotherapy Regimen Prior to Mismatche Allogeneic Stem Cell Transplant

A Phase 2 study testing Venetoclax, Decitabine and Fludarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Northside Hospital, Inc. at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Patients eligible for a mismatch allogeneic stem cell transplant will receive Venetoclax daily for 7 days prior to transplant in addition to the following chemotherapy regimen: Decitabine daily for 5 days, Fludarabine daily for 5 days, and Busulfan daily for 2 days followed by 1 day of total body irradiation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax, Decitabine and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
31 Aug 2024to 31 Aug 2027
Phase
Phase 2
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

  • Availability of a 4/8 - 6/8 HLA-matched related donor or a 7/8 HLA-matched unrelated donor
  • Receiving first allogeneic transplant
  • KPS >/= 70%
  • MDS associated with TP53 mutation AND R-IPSS high or very high risk at diagnosis OR
  • AML with adverse risk cytogenetics or molecular abnormalities according to the 2017 ELN risk stratification OR pre-transplant MRD by either flow cytometry, cytogenetics or FISH
  • Less than 5% myeloblasts in the marrow pre-transplant

Who cannot join

  • Poor cardiac function defined as LVEF <45%
  • Poor pulmonary function defined as FEV1, FVC, or DLCO <50% predicted
  • Poor liver function defined as bilirubin >/=2.5mg/dL, AST/ALT >3xULN
  • Poor renal function defined as creatinine >/=2.0mg/dL or CrCl <40mL/min
  • Ongoing or active systemic infection, active Hepatitis B or C virus infection, or known HIV positivity
  • Patient requiring treatment with a moderate or strong inhibitor or inducer of CYP3A4 or a P-gp inhibitor within 7 days prior to starting preparative chemotherapy through Day +4 post-transplant

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Caitlin Guzowski

    Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: A Phase II Trial of Venetoclax-Enhanced Reduced Intensity HLA-Mismatched Allogeneic Transplant for Ultra-High-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Patients eligible for a mismatch allogeneic stem cell transplant will receive Venetoclax daily for 7 days prior to transplant in addition to the following chemotherapy regimen: Decitabine daily for 5 days, Fludarabine daily for 5 days, and Busulfan daily for 2 days followed by 1 day of total body irradiation. Stem cell transplant will occur thereafter.

Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

Study groups in NCT06337331
Study groupRoleWhat they receive
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell TransplantExperimentalNot described
Receives: Drug: Venetoclax; Drug: Decitabine; Drug: Fludarabine; Drug: Busulfan; Radiation: Total Body Irradiation

What is being measured

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

  1. Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant

    Measured: 12 months

Secondary outcomes (8)

  1. Number of patients alive at one-year post transplant

    Measured: 12 months

  2. Number of patients alive without recurrence of disease at one-year post transplant by conducting blood and bone marrow biopsy procedures

    Measured: 12 months

  3. Number of patients who died one year post-transplant not related to recurrence of disease

    Measured: 12 months

  4. Number of patients who fully engrafted (blood counts fully recovered) by conducting chimerism studies at 30-, 60-, 90-, 180-, and 365-days post transplant

    Measured: 12 months

  5. Number of patients who developed acute graft-versus-host disease by recording signs and symptoms of acute GVHD according to MAGIC standards at one-year post-transplant

    Measured: 12 months

  6. Number of patients who developed chronic graft-versus-host disease by recording signs and symptoms of chronic GVHD according to NIH standards at one-year post-transplant

    Measured: 12 months

  7. Number of patients who are alive at one-year post transplant who also did not develop GVHD

    Measured: 12 months

  8. Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0

    Measured: 12 months

Timeline

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

  1. First posted29 Mar 2024
  2. Study start31 Aug 2024 (estimated)
  3. Primary completion31 Aug 2026 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Why it stopped: Unable to accommodate FDA recommendations for protocol revisions

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06337331
Sponsor's protocol ID
NSH 1401
Status last verified
Jun 2024
First submitted
22 Mar 2024
Last updated
14 Jun 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Estey E, de Lima M, Tibes R, Pierce S, Kantarjian H, Champlin R, Giralt S. Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007 Feb 15;109(4):1395-400. doi: 10.1182/blood-2006-05-021907. Epub 2006 Oct 12.

    PubMed 17038533

  • Stelljes M, Beelen DW, Braess J, Sauerland MC, Heinecke A, Berning B, Kolb HJ, Holler E, Schwerdtfeger R, Arnold R, Spiekermann K, Muller-Tidow C, Serve HL, Silling G, Hiddemann W, Berdel WE, Buchner T, Kienast J; German AML Cooperative Group (AMLCG). Allogeneic transplantation as post-remission therapy for cytogenetically high-risk acute myeloid leukemia: landmark analysis from a single prospective multicenter trial. Haematologica. 2011 Jul;96(7):972-9. doi: 10.3324/haematol.2011.041004. Epub 2011 Apr 1.

    PubMed 21459795

  • Mawad R, Gooley TA, Sandhu V, Lionberger J, Scott B, Sandmaier BM, O'Donnell P, Becker PS, Petersdorf S, Dorcy KS, Hendrie P, Sorror ML, Walter RB, Deeg HJ, Appelbaum FR, Estey EH, Pagel JM. Frequency of allogeneic hematopoietic cell transplantation among patients with high- or intermediate-risk acute myeloid leukemia in first complete remission. J Clin Oncol. 2013 Nov 1;31(31):3883-8. doi: 10.1200/JCO.2013.50.2567. Epub 2013 Sep 23.

    PubMed 24062388

  • Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015 Jul;94(7):1127-38. doi: 10.1007/s00277-015-2351-x. Epub 2015 Mar 20.

    PubMed 25791241

  • Ostgard LSG, Lund JL, Norgaard JM, Norgaard M, Medeiros BC, Nielsen B, Nielsen OJ, Overgaard UM, Kallenbach M, Marcher CW, Riis AH, Sengelov H. Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia: A National Population-Based Cohort Study. Biol Blood Marrow Transplant. 2018 Feb;24(2):314-323. doi: 10.1016/j.bbmt.2017.10.019. Epub 2017 Oct 16.

    PubMed 29051022

  • Joshua TV, Rizzo JD, Zhang MJ, Hari PN, Kurian S, Pasquini M, Majhail NS, Lee SJ, Horowitz MM. Access to hematopoietic stem cell transplantation: effect of race and sex. Cancer. 2010 Jul 15;116(14):3469-76. doi: 10.1002/cncr.25297.

    PubMed 20564154

  • Landry I. Racial disparities in hematopoietic stem cell transplant: a systematic review of the literature. Stem Cell Investig. 2021 Dec 14;8:24. doi: 10.21037/sci-2021-058. eCollection 2021.

    PubMed 35071585

  • Abraham IE, Rauscher GH, Patel AA, Pearse WB, Rajakumar P, Burkart M, Aleem A, Dave A, Bharadwaj S, Paydary K, Acevedo-Mendez M, Goparaju K, Gomez R, Carlson K, Tsai SB, Quigley JG, Galvin JP, Zia M, Larson ML, Berg S, Stock W, Altman JK, Khan I. Structural racism is a mediator of disparities in acute myeloid leukemia outcomes. Blood. 2022 Apr 7;139(14):2212-2226. doi: 10.1182/blood.2021012830.

    PubMed 35061876

  • Bashey A, Zhang X, Morris LE, Holland HK, Bachier-Rodriguez L, Solomon SR, Solh M. Improved access to HCT with reduced racial disparities through integration with leukemia care and haploidentical donors. Blood Adv. 2023 Aug 8;7(15):3816-3823. doi: 10.1182/bloodadvances.2023009765.

    PubMed 36961350

  • Solomon SR, Sizemore CA, Zhang X, Brown S, Holland HK, Morris LE, Solh M, Bashey A. Impact of Donor Type on Outcome after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia. Biol Blood Marrow Transplant. 2016 Oct;22(10):1816-1822. doi: 10.1016/j.bbmt.2016.07.010. Epub 2016 Jul 21.

    PubMed 27453362

  • Fang M, Storer B, Estey E, Othus M, Zhang L, Sandmaier BM, Appelbaum FR. Outcome of patients with acute myeloid leukemia with monosomal karyotype who undergo hematopoietic cell transplantation. Blood. 2011 Aug 11;118(6):1490-4. doi: 10.1182/blood-2011-02-339721. Epub 2011 Jun 16.

    PubMed 21680797

  • Cornelissen JJ, Breems D, van Putten WL, Gratwohl AA, Passweg JR, Pabst T, Maertens J, Beverloo HB, van Marwijk Kooy M, Wijermans PW, Biemond BJ, Vellenga E, Verdonck LF, Ossenkoppele GJ, Lowenberg B. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol. 2012 Jun 10;30(17):2140-6. doi: 10.1200/JCO.2011.39.6499. Epub 2012 May 7.

    PubMed 22564995

  • Middeke JM, Beelen D, Stadler M, Gohring G, Schlegelberger B, Baurmann H, Bug G, Bellos F, Mohr B, Buchholz S, Schwerdtfeger R, Martin H, Hegenbart U, Ehninger G, Bornhauser M, Schetelig J; Cooperative German Transplant Study Group. Outcome of high-risk acute myeloid leukemia after allogeneic hematopoietic cell transplantation: negative impact of abnl(17p) and -5/5q-. Blood. 2012 Sep 20;120(12):2521-8. doi: 10.1182/blood-2012-03-417972. Epub 2012 Jul 31.

    PubMed 22855604

  • Mohr B, Schetelig J, Schafer-Eckart K, Schmitz N, Hanel M, Rosler W, Frickhofen N, Link H, Neubauer A, Schuler U, Platzbecker U, Middeke JM, Ehninger G, Bornhauser M, Schaich M, Stolzel F; Study Alliance Leukaemia (SAL). Impact of allogeneic haematopoietic stem cell transplantation in patients with abnl(17p) acute myeloid leukaemia. Br J Haematol. 2013 Apr;161(2):237-44. doi: 10.1111/bjh.12253. Epub 2013 Feb 21.

    PubMed 23432431

  • Bowen D, Groves MJ, Burnett AK, Patel Y, Allen C, Green C, Gale RE, Hills R, Linch DC. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia. 2009 Jan;23(1):203-6. doi: 10.1038/leu.2008.173. Epub 2008 Jul 3. No abstract available.

    PubMed 18596741

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax, Decitabine and Fludarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Northside Hospital, Inc. 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 6 inclusion and 6 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: withdrawn, as of the sponsor's last update on 14 Jun 2024. 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 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?

The study was withdrawn before enrolling participants, so there are no results.

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 relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant (time frame: 12 months). 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 NCT06337331, which also lists 26 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 14 Jun 2024.

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