Clinical trial NCT06326463: CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies
Official title: CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematologic Malignancy
ALL, Childhood
AML, Childhood
Lymphoma
MDS
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2024-03-22
Enrollment: 24
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose of CD70-CAR T cells
timeFrame: 28 days after CD70-CAR T-cell infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude
name: Swati Naik, MBBS
role: PRINCIPAL_INVESTIGATOR
References: