ALL, Childhood, AML, Childhood, Hematologic Malignancy, Lymphoma, MDS
Conditions
Brief summary
The study participant has one of the following blood cancers: acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (B-ALL, T-ALL) or Lymphoma. Your cancer has been difficult to treat (refractory) or has come back after treatment (relapse). Primary Objective To determine the safety and maximum tolerated dose of intravenous infusions of escalating doses of CD70-CAR T cells in patients (≤21 years) with recurrent/refractory CD70+ hematological malignancies after lymphodepleting chemotherapy. Secondary Objectives To evaluate the antileukemic activity of CD70-CAR T cells. We will determine the anti- leukemic activity of the CD70-CAR T cells in the bone marrow and in the treatment of extramedullary disease.
Detailed description
The primary interventions are a lymphodepleting chemotherapy regimen (fludarabine and cyclophosphamide), followed by a single autologous infusion of CD70-CAR T cells. Phase I study evaluating three (3) dose levels of CD70-CAR T cells.
Interventions
DRUGFludarabine
40mg/m2, Day -4, -3 and -2
DRUGCyclophosphamide
Day -3 and Day-2 REST DAY, -1
DRUGCD70-CAR T cell infusion (Autologous)
Day 0 or +1
DRUGMesna
Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
Age ≤21 years old Relapsed/refractory CD70+ hematological malignancy Relapsed disease: Patients developing recurrent disease after a prior complete remission (CR) Refractory disease: Patients with persistent disease despite 3 cycles of induction chemotherapy. * Relapsed/refractory CD70+ AML or MDS: * Relapsed disease that is CD70 positive * Refractory disease that is persistent despite 3 cycles of chemotherapy * Relapsed/refractory CD70+ B-cell ALL: * Relapsed disease that is CD70 positive and CD19 negative/dim or patients otherwise ineligible for CD19-directed therapies including: * Patients in 2nd or greater relapse * Patients with relapse after allogeneic HSCT * Relapsed/refractory CD70+ T-cell ALL: * Relapsed /refractory disease that is CD70 positive * Mixed Phenotype Acute Leukemia (MPAL): * Relapsed/refractory that is CD70 positive * Relapsed/refractory CD70+ lymphoma: * Relapsed disease that is CD70 positive and CD19 negative/dim or patients otherwise ineligible for CD19-directed therapies including: * Patients in 2nd or greater relapse * Patients with relapse after allogeneic HSCT Estimated life expectancy of \>12 weeks Karnofsky or Lansky (age- dependent) performance score ≥50 Patients with a history of prior allogeneic HCT must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis Patient must have an identified HCT donor For females of childbearing age: i. Not lactating with intent to breastfeed ii. Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment
Exclusion criteria
* Known primary immunodeficiency * Known history of HIV positivity * Severe intercurrent bacterial, viral or fungal infection * History of hypersensitivity to cornstarch or hydroxyethyl starch * Patients with acute promyelocytic leukemia (APL) * Known contraindication to protocol defined lymphodepleting * chemotherapy regimen of Fludarabine/cyclophosphamide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose of CD70-CAR T cells | 28 days after CD70-CAR T-cell infusion | Phase I design to determine the maximum tolerated dose (MTD) of autologous, CD70-CAR T cells. Three (3) dose levels will be evaluated (1x10e6, 3x10e6, and 1x10e7 cells/kg). |
Countries
United States
Contacts
CONTACTSwati Naik, MBBS
PRINCIPAL_INVESTIGATORSwati Naik, MBBS
St. Jude
Outcome results
None listed