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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06326463
• Other study ID #: DIRECT70
• Secondary ID: NCI-2024-03240
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: July 1, 2031

Study information

• Verified date: June 2024
• Source: St. Jude Children's Research Hospital
• Contact: Swati Naik, MBBS
• Phone: 866-278-5833
• Email: referralinfo[@]stjude.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: July 1, 2031
• Est. primary completion date: July 1, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

• 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

Related Conditions & MeSH terms

• ALL, Childhood
• AML, Childhood
• Hematologic Malignancy
• Hematologic Neoplasms
• Lymphoma
• MDS
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Fludarabine
40mg/m2, Day -4, -3 and -2
• Cyclophosphamide
Day -3 and Day-2 REST DAY, -1
• CD70-CAR T cell infusion (Autologous)
Day 0 or +1
• Mesna
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

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of CD70-CAR T cells	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).	28 days after CD70-CAR T-cell infusion

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital