CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies

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.

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