CD123-Directed Autologous or Donor Derived T-Cell Therapy for the Treatment of Relapsed or Refractory Acute Myelogenous Leukemia, CATCH-AML Study
This phase I trial studies the side effects and best dose of CD123 positive chimeric antigen receptor (CAR) T cell therapy in treating patients with acute myelogenous leukemia that has come back (relapsed) or does not respond to treatment (refractory). CAR T-cell therapy is a type of cellular therapy that combines two of the body’s basic disease fighters: antibodies and T-cells. For this type of therapy, peripheral (circulating) immune cells are collected from the patient (autologous) or from a donor (donor derived) and then modified so that they can recognize the antigen, CD123, which is present on the surface of a CD123 positive cancer cell. If the CAR cells ‘see’ the antigen on the cancer cell, they will attack and kill it. CD123 CAR T cells are modified in such a way that allows the T cells to recognize cancer cells, attack, and kill them. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before CD123-directed CAR T-cell therapy may kill more cancer cells.
Inclusion Criteria
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Age =< 21 years old
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Relapsed/refractory CD123+ disease defined as follows: * AML/myelodysplastic syndrome (MDS) ** Relapsed disease: Patients developing recurrent disease after a prior complete remission (CR) ** Refractory disease: Patients with persistent disease despite 2 cycles of induction chemotherapy * B-cell ALL ** Relapsed disease that is CD123 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 *** Refractory disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies * T-cell ALL ** Relapsed /refractory disease that is CD123 positive * Mixed phenotype acute leukemia (MPAL) ** Relapsed/refractory that is CD123 positive * BPDCN ** Relapsed/refractory disease that has failed front-line therapy
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Estimated life expectancy of > 12 weeks
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Karnofsky or Lansky (age-dependent) performance score >= 50
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Patients with a history of prior allogeneic hematopoietic cell transplantation (HCT) must be clinically recovered from prior HCT therapy, have no evidence of active graft versus host disease (GVHD) and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Patient must have an identified, suitable HCT donor
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: For females of child bearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY (FOR PATIENTS ON ARM A): Meets eligibility criteria to undergo autologous apheresis, or have a previously frozen, autologous leukapheresis product that can be used for T-cell production
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY (FOR PATIENTS ON ARM B): Have an available donor that meets donor criteria
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): A previously frozen, leukapheresis product can be used for T-cell production
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): Identified recipient with relapsed and/or refractory CD123-positive hematological malignancy
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): Allogeneic donor of previous transplant for recipient and at least a haploidentical donor with 4/8 HLA matching to the recipient
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): HIV negative
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): For females of child bearing age: * Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment; AND * Not lactating with intent to breastfeed
- DONOR APHERESIS AND MANUFACTURING ELIGIBILITY (ARM B): Regarding donation eligibility, is identified as either: * Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR * Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Age =< 21 years old a the time of manufacturing
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Detectable disease that is CD123+ (at least minimal residual disease [MRD]+ disease)
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Estimated life expectancy of > 8 weeks
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Karnofsky or Lansky (age-dependent) performance score >= 50
- TREATMENT ELIGIBILITY (ARM A AND ARM B): 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 planned infusion
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Patient must have an identified, suitable HCT donor
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Adequate cardiac function defined as left ventricular ejection fraction > 40%, or shortening fraction >= 25%
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Electrocardiogram (EKG) without evidence of clinically significant arrhythmia
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Adequate renal function defined as creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 50 ml/min/1.73 m^2 (GFR >= 40 ml/min/1.73 m^2 if < 2 years of age)
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Adequate pulmonary function defined as forced vital capacity (FVC) >= 50% of predicted value; or pulse oximetry >= 92% on room air if patient is unable to perform pulmonary function testing
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Total Bilirubin =< 3 times the upper limit of normal for age, except in subjects with Gilbert’s syndrome
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 5 times the upper limit of normal for age
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Has recovered from all National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade III-IV, non-hematologic acute toxicities from prior therapy
- TREATMENT ELIGIBILITY (ARM A AND ARM B): For females of child bearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
- TREATMENT ELIGIBILITY (ARM A AND ARM B): If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Available transduced T-cell product that has met good manufacturing practice (GMP) release criteria
Exclusion Criteria
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Known primary immunodeficiency
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: History of human immunodeficiency virus (HIV) infection
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Severe intercurrent uncontrolled bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: History of hypersensitivity reactions to murine protein-containing products
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: History of severe hypersensitivity reactions to cornstarch or hydroxyethyl starch
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Patients with acute promyelocytic leukemia (APL, t[15;17])
- PROCUREMENT AND T-CELL PRODUCTION ELIGIBILITY: Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Known primary immunodeficiency
- TREATMENT ELIGIBILITY (ARM A AND ARM B): History of HIV infection
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Severe intercurrent uncontrolled bacterial, viral or fungal infection
- TREATMENT ELIGIBILITY (ARM A AND ARM B): History of hypersensitivity reactions to murine protein-containing products
- TREATMENT ELIGIBILITY (ARM A AND ARM B): History of severe hypersensitivity reactions to cornstarch or hydroxyethyl starch
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to CD123-CAR T cell infusion
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Receiving systemic therapy in the 14 days prior to CD123-CAR T-cell infusion, which will interfere with the activity of the CD123-CAR T cells in vivo (in the opinion of the study principal investigator [PI][s])
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Receiving rituximab therapy in the 30 days prior to CD123-CAR T-cell infusion. (This exclusion criterion is intended to prevent premature exposure of CD123-CAR T-cells to rituximab, which would activate the safety switch and promote CAR T-cell apoptosis)
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Receiving intrathecal chemotherapy in the 7 days prior to CD123-CAR T-cell infusion
- TREATMENT ELIGIBILITY (ARM A AND ARM B): Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide
Additional locations may be listed on ClinicalTrials.gov for NCT04318678.
Locations matching your search criteria
United States
Tennessee
Memphis
PRIMARY OBJECTIVES:
I. To determine the safety of one intravenous infusion of escalating doses of autologous, CD123-CAR T cells in patients (=< 21 years) with recurrent/refractory CD123+ disease (acute myeloid leukemia [AML], B-acute lymphoblastic leukemia [ALL], T-ALL, blastic plasmacytoid dendritic cell neoplasm [BPDCN] or mixed phenotype acute leukemia [MPAL]) after lymphodepleting chemotherapy.
II. To determine the safety of an intravenous infusion of escalating doses of donor derived, CD123-CAR T cells in patients (≤ 21 years) with recurrent/refractory CD123+ disease (AML/ myelodysplastic syndrome [MDS], B-ALL, T-ALL, BPDCN or MPAL) after lymphodepleting chemotherapy.
SECONDARY OBJECTIVE:
I. To evaluate the anti-leukemia activity of CD123-CAR T cells.
EXPLORATORY OBJECTIVES:
I. To assess the immunophenotype, clonal structure and endogenous repertoire of CD123-CAR T cells and unmodified T cells.
II. To characterize the cytokine profile in the peripheral blood and cerebrospinal fluid (CSF) after treatment with CD123-CAR T cells.
III. To characterize tumor cells post CD123-CAR T-cell therapy.
IV. To compare in vivo properties of donor-derived versus autologous CD123-CAR T cells.
OUTLINE: This is a dose-escalation study of autologous anti-CD123 CAR-T cells. Patients who have not received an allogeneic transplant or for patients who have received allogeneic transplant and do not have a transplant donor available are assigned to arm A, patients who relapsed following allogeneic transplant and whose CAR T-cells will be manufactured from the previous transplant donor are assigned to arm B.
ARM A: Patients receive standard of care lymphodepletion chemotherapy consisting of fludarabine intravenously (IV) on days -4 to -2 for 3 doses and cyclophosphamide IV on days -3 to -2 for 2 doses in the absence of disease progression or unacceptable toxicity. At days 0 or 1, patients receive autologous anti-CD123 CAR-T cells IV over 30 minutes in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography on study and bone marrow aspiration and biopsy, lumbar puncture and blood and cerebrospinal fluid collection throughout the study.
ARM B: Patients receive standard of care lymphodepletion chemotherapy consisting of fludarabine IV on days -4 to -2 for 3 doses and cyclophosphamide IV on days -3 to -2 for 2 doses in the absence of disease progression or unacceptable toxicity. At days 0 or 1, patients receive donor derived anti-CD123 CAR-T cells IV over 30 minutes in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography on study and bone marrow aspiration and biopsy, lumbar puncture and blood and cerebrospinal fluid collection throughout the study.
After the completion of study treatment, patients are followed up to 1 year and then up to 15 years as part of the long-term follow-up protocol.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorSwati Naik
- Primary IDCATCHAML
- Secondary IDsNCI-2020-02416
- ClinicalTrials.gov IDNCT04318678