Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04000698
Other study ID # NCPHOI-2018-08
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date October 15, 2019
Est. completion date December 2022

Study information

Verified date November 2020
Source Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Contact Larisa Shelikhova
Phone 84956647078
Email larisa.shelikhova@fccho-moscow.ru
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias


Description:

The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity. The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia. Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.


Recruitment information / eligibility

Status Recruiting
Enrollment 25
Est. completion date December 2022
Est. primary completion date July 2022
Accepts healthy volunteers No
Gender All
Age group N/A to 25 Years
Eligibility Inclusion Criteria: 1. Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent 2. Disease stage - Acute myeloid leukemia (AML), relapsed or refractory, failure to achieve hematologic remission after at least to courses of intensive chemotherapy, including at least one course with high-dose AraC and fludarabine - Acute lymphoblastic leukemia (ALL), relapsed or refractory, failure to achieve hematologic remission after at least two high-dose therapy blocks 3. Patient eligible for current hematopoietic stem cell transplantation protocol 4. The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry 5. CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry 6. CD184 7. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis. 8. Patient Clinical Performance Status: Karnofsky >50% or Lansky >50% 9. Patient Life Expectancy >12 weeks 10. Patients who agree to long-term follow up for up to 5 years Exclusion Criteria: - Age >25 years - Patients with uncontrolled infections - Clearance of creatinine < 70 ml/min - Cardiac ejection fraction < 40% - Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air - Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal - Karnofsky/Lansky Scale <70%

Study Design


Related Conditions & MeSH terms

  • Leukemia
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Acute Myeloid Leukemia

Intervention

Drug:
Preparative regimen
Preparative chemotherapy before allogeneic HSCT Fludarabin Cytarabine Venetoclax Daratumomab Vecanoid Condition treosulfan fludarabine thiophosphomide Venetoclax Plerixafor GVHD prophylaxis abatacept tocilizumab rituximab HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes

Locations

Country Name City State
Russian Federation Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology Moscow

Sponsors (1)

Lead Sponsor Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type Measure Description Time frame Safety issue
Primary cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT 30 days after HSCT
Primary Overall response rate Proportion of patients with hematologic remission at time points 30 days after HSCT
Primary Partial response rate Proportion of patients with MRD negativity at time points 30 days after HSCT
Primary Rate of toxicity stage > 3 according to CTCAE 5.0 Proportion of patients with allergic/ anaphylaxis reaction toxicity stage > 3 according to CTCAE 5.0 40 days after first drug administration
Primary cumulative incidence of transplant-related mortality 100 days after HSCT
Secondary Rate of expression of target molecule on blast cells Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2 1 week before first drug administration
Secondary cumulative incidence of acute GVHD grade II-IV 120 days after HSCT
Secondary cumulative incidence of chronic GvHD 1 year after HSCT
Secondary Rate of immune recovery at day 30 Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell >determined numbers 30
Secondary overall survival 1 year after HSCT
Secondary event-free survival 1 year after HSCT
See also
  Status Clinical Trial Phase
Active, not recruiting NCT02890329 - Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia Phase 1
Active, not recruiting NCT04975919 - Venetoclax in Combination With Decitabine and Cedazuridine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Terminated NCT02882321 - Oxidative Phosphorylation Inhibitor IACS-010759 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Recruiting NCT03214562 - Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Active, not recruiting NCT03289910 - Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia Phase 2
Completed NCT02756572 - Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms Phase 2
Completed NCT02509546 - 8-Chloroadenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Recruiting NCT03683433 - Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation Phase 2
Completed NCT02551718 - High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia N/A
Completed NCT02070458 - Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Terminated NCT03557970 - JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Recruiting NCT03661307 - Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome Phase 1/Phase 2
Recruiting NCT03629171 - Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia Phase 2
Recruiting NCT05396859 - Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia Phase 1
Terminated NCT03067571 - Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Phase 2
Completed NCT04146038 - Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease Phase 2
Suspended NCT03128034 - 211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia Phase 1/Phase 2
Active, not recruiting NCT04207190 - Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia Phase 1
Recruiting NCT04047641 - Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Phase 1/Phase 2
Withdrawn NCT04493099 - Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML Phase 1/Phase 2