Venetoclax Plus RIC Regimen Allo-HSCT for Elderly Patients With High-risk Myeloid Malignancies

NCT05583175 | Unknown Phase 2

• 1 other identifier: SHSYXY-202202-VEN-RIC
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single center, single arm, prospective, phase II clinical study to evaluate the efficacy and safety of Venatoclax combined with reduced intensity conditioning regimen allo-HSCT in the treatment of high-risk myeloid malignancies in the elderly patients.

Conditions

Leukemia, Myeloid, Acute; MDS; Hematopoietic Stem Cell Transplantation; Myeloid Malignancy

Outcome Measures

Primary Outcomes (2)

• PFS

  Progression free survival for all patients enrolled

  1- year PFS

• PFS

  Progression free survival for all patients enrolled

  2- year PFS

Secondary Outcomes (10)

• OS

  1- year OS

• OS

  2- year OS

• aGVHD rate

  180 days after transplantation

• cGVHD rate

  1 year after transplantation

• cGVHD rate

  2 years after transplantation

Study Arms (1)

Venetoclax plus RIC

EXPERIMENTAL

Administration with oral Venetoclax plus RIC regimen for allo-HSCT in the elderly patients with myeloid malignancies.

Drug: Venetoclax plus RIC

Interventions

Venetoclax plus RIC DRUG

Eligible patients will receive Venetoclax plus RIC regimen allogeneic transplantation. The treatment regimen is: Venetoclax 100mg/d - 10d, 200mg/d - 9d (first use and NR or untreated MDS), 400mg/d, - 8d\~ - 2d (7d); Fludarabine: 30mg/m2/d, - 6d\~-2d (5d), Cytarabine: 1g/m2/d, - 6d\~-2d (5d) Busulfan: 3.2mg/m2/d, - 6d\~-5d (2d), TBI: 3 Gray, - 1d.

Venetoclax plus RIC

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 55 years old;
• High risk myeloid malignancies： 1）No hematological remission(NR) after induction/re-induction treatment for AML; 2）Morphological remission but with persistent positive minimal resident disease(MRD) (Flow cytometry\>0.01% and/or fusion gene positive and/or digital polymerase chain reaction(PCR) positive）; 3）High risk acute myeloid leukemia(AML) according to 2022 European Leukemia Net(ELN) risk stratification； 4）High risk myelodysplastic syndrome(MDS): IPSS-R score ≥ middle risk-2; therapy-related MDS; MDS with mutation of ASXL1, EZH2, RUNX1, SRSF2, U2AF1, STAG2, NRAS, ZRSR2, or TP53； 5）High risk chronic myelomonocytic leukemia(CMML), MDS/MPN.
• Patients must have appropriate donor:
• ）Related donor must be HLA-A, - B, - C, - DQB1 and - DRB1 matched at least 5/10; 2）Unrelated donor must be HLA-A, - B, - C, - DQB1 and - DRB1 matched at least 8/10; 4. Hematopoietic cell transplantation-comorbidity Index(HCT-CI) score ≤ 4。 5. Eastern Cooperative Oncology Group(ECOG) score 0-2。 6. Liver, kidney and cardiopulmonary functions meet the following requirements:
• Creatinine≤1.5×ULN;
• Left ventricular ejection fraction \>50%;
• Baseline oxygen saturation\>92%;
• Total bilirubin≤1.5×ULN；ALT and AST≤2.0×ULN；
• DLCO≥ 40% and FEV1 ≥ 50%。 7. Able to understand and sign the Informed Consent Document.

You may not qualify if:

• Patients with Venetoclax ineffectiveness;
• Malignant tumors other than acute myeloid leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection；
• ECOG socre\>2;
• HCT-CI score\> 4。
• Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 3 months prior to screening), myocardial infarction (within 3 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; patients with pulmonary hypertension
• Uncontrolled infection during screening period; Hemodynamic instability associated with infection,a new infection or aggravation of the original infection;new lesions on imaging;fever of unknown cause;
• Patients with symptoms of central nervous system;greater than grade 2 requiring treatment,paralysis,aphasia,acute cerebral infarction,severe traumatic brain injury,schizophrenia;
• HIV infection;
• Patients with active hepatitis B virus (HBV) and active hepatitis C virus (HCV) need antiviral treatment; Patients at risk of HBV activation refer to patients with positive HBsAg or HBeAb but not receiving anti-HBV treatment;
• History of autoimmune disease；
• Pregnant or lactating women；
• Fertile men and women who are unwilling to use contraceptive technology during the treatment period and within 12 months after treatment.

Sponsors & Collaborators

• Xianmin Song, MD: lead

Study Sites (1)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

Related Publications (1)

• Garcia JS, Kim HT, Murdock HM, Cutler CS, Brock J, Gooptu M, Ho VT, Koreth J, Nikiforow S, Romee R, Shapiro R, Loschi F, Ryan J, Fell G, Karp HQ, Lucas F, Kim AS, Potter D, Mashaka T, Stone RM, DeAngelo DJ, Letai A, Lindsley RC, Soiffer RJ, Antin JH. Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active. Blood Adv. 2021 Dec 28;5(24):5536-5545. doi: 10.1182/bloodadvances.2021005566.

  PMID: 34614506 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Xianmin Song

  Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Gao

CONTACT

+86177882248225; siberia77@qq.com

Xianmin Song

CONTACT

+862163240090; shongxm@139.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Hematology

Study Record Dates

• First Submitted: October 9, 2022
• First Posted: October 17, 2022
• Study Start: November 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)