Clinical trial NCT04959903: Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Hematological Malignancies After T Cell Depleted Allo-HSCT
Official title: A Phase I/II Study Evaluating the Safety and the Efficacy of SMART101 Injection to Accelerate Immune Reconstitution After T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Adult Patients With Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancies
Lead sponsor: Smart Immune SAS
Sponsor class: INDUSTRY
First posted: 2021-07-13
Enrollment: 36
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitor (HTLP)) injection to accelerate immune reconstitution after T cell depleted allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients with hematological malignancies.


Eligibility criteria: Inclusion Criteria:

Group A (adults):

1. Adult patients affected by:

   * Acute leukemia (AML, ALL) defined as:

     * Acute Myeloid Leukemia (AML):

       * High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities
       * Chemo-refractory relapse (MRD+)
       * ≥ CR2
     * Acute Lymphoblastic Leukemia (ALL):

       * Chemo-refractory relapse (MRD+)
       * High risk ALL in CR1; Philadelphia (like) or any poor risk feature
       * ≥ CR2
     * Acute leukemia of ambiguous lineage:

       * ≥ CR1 with a minimal residual disease (MRD) \<5% (flow cytometry, molecular and/or cytogenetics accepted)
   * Myelodysplastic Syndrome (MDS) with least one of the following:

     * Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
     * Life-threatening cytopenia.
     * Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
     * Therapy related disease or disease evolving from other malignant processes.
2. Patient eligible for a T-depleted allogeneic HSCT
3. Age ≥ 18y and clinical condition compatible with allogeneic stem cell transplantation
4. Karnofsky index ≥ 70% prior to conditioning regimen
5. Patients with normal organ function prior to conditioning regimen

Group B (pediatrics):

1. Pediatric patients affected by acute leukemia defined as:

   * Acute Myeloid Leukemia (AML):

     * High risk AML in CR1; any adverse genetic abnormality, secondary or therapy related AML excluding good risk genetic abnormalities,
     * Chemo-refractory relapse (MRD+)
     * ≥ CR2
   * Acute Lymphoblastic Leukemia (ALL):

     * Chemo-refractory relapse (MRD+)
     * High risk ALL in CR1; Philadelphia (like) or any poor risk feature
     * ≥ CR2
   * Acute leukemia of ambiguous lineage:

     * ≥ CR1 with a minimal residual disease (MRD) \<5% (flow cytometry, molecular and/or cytogenetics accepted)
2. Patient eligible for a T-depleted allogeneic HSCT
3. Age \< 18y at the time of inclusion
4. Absence of a matched sibling donor (MSD)
5. Lansky ≥ 70% / Karnofsky performance status ≥ 70% prior to conditioning regimen
6. Patients with normal organ function prior to conditioning regimen

Exclusion Criteria:

Groups A and B:

1. Use of an HLA matched Cord Blood (8/8 allele matched) or haploidentical donor
2. Prior therapy with allogeneic stem cell transplantation
3. Treatment with another cellular therapy within one month before inclusion

Primary outcomes:
measure: Cumulative incidence of grade III-IV GvHD
timeFrame: 100 days post-HSCT
measure: Occurrence of adverse events related to SMART101
timeFrame: 100 days post-HSCT
measure: CD4+ T cell count
timeFrame: 100 days post-HSCT
Secondary outcomes:
measure: T cell immune reconstitution
timeFrame: up to Month 12 post-HSCT
measure: Cumulative incidence of infections
timeFrame: Day 90, and Months 6, 12 and 24 post-HSCT
measure: Non-relapse mortality (NRM)
timeFrame: Day 90, and Months 6, 12 and 24 post-HSCT
Other outcomes:
measure: Overall Survival (OS)
timeFrame: Month 24 post-HSCT
measure: Disease-free Survival
timeFrame: Month 24 post-HSCT
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center (MSKCC)
name: Jaap-Jan BOELENS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: