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.
Eligibility Criteria
Age Range: No minimum to 21 years
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
Interventions
DRUG
Fludarabine
DRUG
Cyclophosphamide
DRUG
CD70-CAR T cell infusion (Autologous)
DRUG
Mesna