Use of T-allo10 Cell Infusions Combined With Mismatched Related or Mismatched Unrelated Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies

Overview

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.
SparkCures ID 1634
Trial Phase Phase 1
Enrollment 5 Patients
Treatments
Trial Collaborators
  • National Cancer Institute (NCI)
NCT Identifier

NCT03198234

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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

US Trial Locations

Please visit the ClinicalTrials.gov page for historical site information.

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