Stem Cell Transplant + Immunotherapy for Blood Cancers

Recruiting in Palo Alto (17 mi)

Overseen byBrandon Triplett, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time. The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment. This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival.

Research Team

Brandon Triplett, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults up to 21 years old with high-risk blood cancers like leukemia or lymphoma, who are in remission but at risk of relapse. They must have a partially matched family donor available quickly, be HIV negative, not pregnant or breastfeeding, and their major organs must function well. It's not open to those with other active cancers or who've had certain transplants within the last year.

Inclusion Criteria

Patient must fulfill pre-transplant organ function criteria: Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%. Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2. Forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing. Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See APPENDIX A). Bilirubin ≤ 3 times the upper limit of normal for age. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age. Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment. Not breast feeding. Does not have current uncontrolled bacterial, fungal, or viral infection.

Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).

My blood cancer is considered high risk, with specific genetic features or poor response to initial treatment.

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Exclusion Criteria

N/A

Treatment Details

Interventions

ATG (rabbit) (Other)
Blinatumomab (CAR T-cell Therapy)
CD45RA-depleted DLI (Other)
CliniMACS (Other)
Cyclophosphamide (Other)
Fludarabine (Other)
G-csf (Other)
Melphalan (Other)
Mesna (Other)
TCRα/β+ (Other)
Thiotepa (Other)

Trial OverviewThe study tests a transplant using blood cells from a family member that have been modified in the lab to reduce graft-vs-host disease risk. These cells lack TCRαβ proteins known for causing this complication. After engraftment, patients receive an additional infusion of memory T-cells from the donor. The effects on patient survival and cancer recurrence are being studied alongside chemotherapy drugs used.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Transplant participantsExperimental Treatment12 Interventions

Participants receive a conditioning regimen of ATG (rabbit),Cyclophosphamide 60 mg/kg intravenous once daily, mesna, fludarabine, thiotepa, melphalan, followed by HPC,A Infusion(TCRα/β+ and CD19+ depleted),HPC, A infusion (if needed to achieve goal CD34+ cell dose.CD45RA-depleted DLI will be given at least two weeks after engraftment. Blinatumomab will be given at least one week post-DLI, and only to patients with CD19+ malignancies. G-csf 5mcg/kg subcutaneous or intravenous daily until ANC \>2000 for 2 consecutive days. Cells for infusion are prepared using the CliniMACS system.

Cyclophosphamide is already approved in Canada, Japan for the following indications: