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CART123 Cells With or Without Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia

ConditionAcute Myeloid Leukemia (AML)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age0-29
SponsorStephan Grupp MD PhD

About this trial

This study is designed to evaluate the safety and effectiveness of CART123 cells either alone or when combined with ruxolitinib in pediatric and young adult subjects with relapsed or refractory AML. Subjects will be enrolled into one of two treatment cohorts: subjects who will receive CART123 alone (Cohort A) or subjects who will receive CART123 in combination with ruxolitinib (Cohort B).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

1. Age at time of consent: Cohort A: 0-29 years. Cohort B: 1-29 years (Note: the first subject at each dose level of Cohort B must be ≥12 years old)

Second or greater relapse defined as bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy after second documented complete remission; OR

Any detectable disease post-allogeneic transplant with bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy; OR

Refractory disease, defined as: Persistent bone marrow involvement with ≥0.1% disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after two courses of induction chemotherapy for patients at initial presentation, ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of induction chemotherapy for patients who have relapsed after previously achieving a CR , and ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of AML-directed chemotherapy for those with myeloid lineage switch.

Disqualifiers

1. Active hepatitis B or active hepatitis C

2. HIV infection

3. Active acute or chronic GVHD requiring systemic therapy

4. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Anti-CD123 LV redirected T cells (CART123)

    Biological/Vaccine

    CART123 cells: lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains.

  • Ruxolitinib (JAKAVI®)

    Drug

    Ruxolitinib: an orally administered janus-activated kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2.

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Cohort AExperimental treatment 1 intervention
Group B: Cohort BExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Evaluate the Safety of CART123

Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123

Time frame
5 years
2

Safety of CART123 in combination with Ruxolitinib

Frequency of Adverse events will be measured by evaluating the frequency and severity of treatment related adverse events following administration of CART123 and Ruxolitinib

Time frame
5 Years
3

Determine Maximum Tolerated Dose of CART123

The Maximum Tolerated Dose will be determined by measuring the incidence of dose limiting toxicities following administration of the CART123 product.

Time frame
5 years

Secondary outcomes

1

Determine Feasibility of CART123 Treatment

Measured by the proportion of enrolled subjects who receive CART123 infusion.

Time frame
5 years
2

Determine feasibility of combination treatment with CART123 and ruxolitinib

Measured by the rate of enrolled subjects who receive CART123 infusion and at least 7 days of ruxolitinib.

Time frame
5 years
3

Determine the Preliminary Efficacy of CART123

Measured by the rate of subjects who achieve complete remission following treatment with CART123 at Day 28.

Time frame
5 years
4

Determine the Preliminary Efficacy of CART123 + Ruxolitinib

Measured by the rate of subjects who achieve complete remission following treatment with CART123 and at least 7 days of Ruxolitinib at Day 28.

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stephan Grupp MD PhD

Lead sponsor

Children's Hospital of Philadelphia

Sponsor institution

Children's Hospital of Philadelphia

Collaborator

Source ClinicalTrials.gov
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