Clinical Trials /

Use of T-allo10 in Hematopoietic Stem Cell Transplantation (HSCT) for Blood Disorders

NCT03198234

Description:

A significant number of patients with hematologic malignancies need a hematopoietic stem cell transplant (HSCT) to be cured. Only about 50% of these patients have a fully matched donor, the remaining patients will require an HSCT from a mismatched related or unrelated donor. Almost 60% of these mismatched donor HSCTs will result in graft-versus-host disease (GvHD), which can cause significant morbidity and increased non-relapse mortality. GvHD is caused by the donor effector T cells present in the HSC graft that recognize and react against the mismatched patient's tissues. Researchers and physicians at Lucile Packard Children's Hospital, Stanford are working to prevent GvHD after HSCT with a new clinical trial. The objective of this clinical program is to develop a cell therapy to prevent GvHD and induce graft tolerance in patients receiving mismatched unmanipulated donor HSCT. The cell therapy consists of a cell preparation from the same donor of the HSCT (T-allo10) containing T regulatory type 1 (Tr1) cells able to suppress allogenic (host-specific) responses, thus decreasing the incidence of GvHD. This is the first trial of its kind in pediatric patients and is only available at Lucile Packard Children's Hospital, Stanford. The purpose of this phase 1 study is to determine the safety and tolerability of a cell therapy, T-allo10, to prevent GvHD in patients receiving mismatched related or mismatched unrelated unmanipulated donor HSCT for hematologic malignancies.

Related Conditions:
  • Acute Myeloid Leukemia
  • B-Cell Acute Lymphoblastic Leukemia
  • Hodgkin Lymphoma
  • Mixed Phenotype Acute Leukemia
  • Myelodysplastic Syndrome with Excess Blasts-2
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
  • Secondary Acute Myeloid Leukemia
  • T-Cell Acute Lymphoblastic Leukemia
  • Therapy-Related Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03198234

Trial Eligibility

Document

Title

  • Brief Title: Use of T-allo10 in Hematopoietic Stem Cell Transplantation (HSCT) for Blood Disorders
  • Official Title: Use of T-allo10 Cell Infusions Combined With Mismatched Related or Mismatched Unrelated Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: SU-IRB-38734
  • NCT ID: NCT03198234

Conditions

  • AML - Acute Myeloid Leukemia
  • MDS (Myelodysplastic Syndrome)
  • Mixed Phenotype Acute Leukemia
  • NHL - Non-Hodgkin's Lymphoma
  • Hodgkin's Lymphoma
  • ALL

Interventions

DrugSynonymsArms
T-allo10Cohort 1

Purpose

A significant number of patients with hematologic malignancies need a hematopoietic stem cell transplant (HSCT) to be cured. Only about 50% of these patients have a fully matched donor, the remaining patients will require an HSCT from a mismatched related or unrelated donor. Almost 60% of these mismatched donor HSCTs will result in graft-versus-host disease (GvHD), which can cause significant morbidity and increased non-relapse mortality. GvHD is caused by the donor effector T cells present in the HSC graft that recognize and react against the mismatched patient's tissues. Researchers and physicians at Lucile Packard Children's Hospital, Stanford are working to prevent GvHD after HSCT with a new clinical trial. The objective of this clinical program is to develop a cell therapy to prevent GvHD and induce graft tolerance in patients receiving mismatched unmanipulated donor HSCT. The cell therapy consists of a cell preparation from the same donor of the HSCT (T-allo10) containing T regulatory type 1 (Tr1) cells able to suppress allogenic (host-specific) responses, thus decreasing the incidence of GvHD. This is the first trial of its kind in pediatric patients and is only available at Lucile Packard Children's Hospital, Stanford. The purpose of this phase 1 study is to determine the safety and tolerability of a cell therapy, T-allo10, to prevent GvHD in patients receiving mismatched related or mismatched unrelated unmanipulated donor HSCT for hematologic malignancies.

Detailed Description

      Patients ages 3-30 years, with hematologic malignancies undergoing mismatched related or
      unrelated donor transplant will receive conditioning chemotherapy with Total body radiation
      and cyclophosphamide, according to the standard procedure.

      The investigators plan to infuse the donor T-allo10 product one day before HSCT so that the
      Tr1 cells contained within the T-allo10 product will be able to prevent anti-host
      alloreactivity of the T cells present within the unmanipulated HSC graft. Indeed, Tr1 cells
      best exert their suppressive activity at the time of effector T cell activation, occurring
      when the T cells present in the HSC graft will be transferred to the patient ; therefore, the
      investigators expect that the early infusion of T-allo10 cells will optimally modulate
      anti-host alloreactivity of the donor T cells and prevent GvHD.

      Immunosuppression will also be administered at the time of HSCT.

      Up to 27 eligible patients will be given the T-allo10 product sequentially in 3 escalating
      dose cohorts to determine the maximum tolerated dose (or the highest dose tested if no
      maximum tolerated dose is reached). Each cohort will begin by evaluating 3 patients. The
      patients in each cohort will be staggered by 28 days and each succeeding patient will be
      enrolled no sooner than the 29 day after the preceding patient's infusion of T-allo10.

        -  If no patient in a cohort develops a dose limiting toxicity (DLT) following infusion of
           the investigational cellular product, the investigators will start enrolling patients at
           the next higher cell dose after completing the 28-day safety evaluation of the 3rd
           patient in the dose cohort.

        -  If one out of 3 patients in a cohort has a DLT, 3 additional patients will be evaluated
           at the same dose level.

        -  If one out of 6 patients experiences a DLT, dose escalation will occur.

        -  If 2 out of ≤ 6 patients experience a DLT, dose escalation will cease and that dose will
           be designated the maximally administered dose.

        -  Up to three (3) additional patients will be entered at the next lowest dose level if
           only 3 patients were treated previously at that dose

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalParticipants will receive 1 X 10^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)
  • T-allo10
Cohort 2ExperimentalParticipants will receive 3 X 10^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)
  • T-allo10
Cohort 3ExperimentalParticipants will receive 9 X 10^6/kg (± 10%) T-allo10 cells infused intravenously on Day -1 (day before transplant)
  • T-allo10

Eligibility Criteria

        Inclusion Criteria:

          1. Eligible diseases include:

             A. Acute Lymphoblastic Leukemia (B- or T-ALL)

               1. Complete Response (CR)1-ultra high risk features

                    -  Unfavorable cytogenetics

                    -  Hypodiploidy

                    -  Induction failure

                    -  Minimal Residual Disease (MRD) positive after consolidation

               2. CR-2:

                    -  Any of the high risk features listed in CR1

                    -  B-ALL: any relapse considered eligible for transplant

                    -  T- ALL

               3. CR-3-any

             B. Acute Myeloid Leukemia

               1. MRD >5% at day 22 induction 1

               2. MRD >0.1% after induction 2

               3. FLT/ITD with allelic ratio > 0.4 and MRD >0.1% at day 22 or 29 induction 1

               4. Translocation (6:9), (8:6), (16:21), monosomy 7, monosomy 5, 5q

               5. M7 with KMT2A rearrangements, inv(16)(p13.3q24.3) [CBFA2T3-GLIS2] or
                  t(11;12)(p15;p13) [NUP98-KDM5A]

               6. AML in 2nd or subsequent CR

               7. Therapy related or Secondary AML

               8. Refractory anemia with excess blasts (RAEB)2

             C. Myelodysplastic syndrome D. Mixed Phenotype Acute Leukemia MRD>1% after
             consolidation E. Non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL) beyond first
             remission

          2. Age ≥3 to ≤45 years old. Subjects 1 and 2 (in Cohort 1) will be ≥ 12 years old

          3. Available mismatched related donor (mMRD) or mismatched unrelated donor (mMUD), Human
             leukocyte antigen (HLA) matched 8/10 or 9/10

          4. Lansky (age <16) or Karnofsky (age ≥16) performance status ≥80%

          5. Able and willing to provide written, signed informed consent (assent as appropriate)

          6. Have adequate organ function defined as the following:

               -  Serum Creatinine <1.5 X upper limit of normal (ULN) or 24-hour creatinine
                  clearance >50 ml/min

               -  Serum bilirubin ≤ 2 x ULN

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)

                  ≤10 x ULN

               -  Diffusion Capacity of the Lungs (DLCO) >60% predicted (in children, O2 saturation
                  >92% on room air)

               -  Left ventricular ejection fraction >45% (in children, shortening fraction >26%)

          7. Male and female subjects of child bearing potential must agree to use an effective
             method of birth control to avoid pregnancy throughout the transplant procedure, while
             on immunosuppression, and if the subject experiences any chronic GvHD.

        Exclusion Criteria:

          1. Prior bone marrow or peripheral blood HSCT within the last 6 (six) months

          2. HLA-matched related or unrelated donor available

          3. Any active, uncontrolled infection at the time of enrollment

          4. Pregnant or lactating females

          5. Any severe concurrent disease which, in the judgement of the investigator, would place
             the patient at increased risk during participation in the study

          6. Any subject with a history of significant renal, hepatic, pulmonary, or cardiac
             dysfunction or on treatment to support cardiac dysfunction

          7. HIV positive

          8. Non-cooperative behavior or non-compliance of the patient and/or of his/her family

          9. Received another investigational agent within 30 days of enrollment

         10. Patients with Down's syndrome
Maximum Eligible Age:45 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment emergent adverse events (TEAE)
Time Frame:Time of T-allo10 cell infusion until 28 days following the infusion.
Safety Issue:
Description:Assessments of TEAE will include laboratory abnormalities, changes in vital signs, and changes in physical examination following infusion of T-allo10 cells in order to assess the tolerability of T-allo10.

Secondary Outcome Measures

Measure:Incidence and severity of grade III and IV acute GvHD
Time Frame:Study visits through Day +100
Safety Issue:
Description:The incidence of grade III and IV acute GvHD at Day +100 following infusion of Tallo10 cells, assessed using the Modified Keystone scale administered by an independent evaluator on study visits through Day +100

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stanford University

Trial Keywords

  • Pediatric
  • GvHD
  • Hematopoietic Stem Cell Transplantation
  • Stem Cells
  • Transplant
  • BMT - bone marrow transplant

Last Updated

June 28, 2021