Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Lentivirally Redirected CD123 Autologous T Cells in AML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03766126
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in Acute Myeloid Leukemia (AML) subjects.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia, in Relapse Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Refractory Biological: CART123 cells; cyclophosphamide; fludarabine Phase 1

Detailed Description:

This is a phase 1 study to determine the safety, feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with IV administration of CART123 cells using a split dosing approach (10% Day 0, 30% Day 1; 60% Day 2).

The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose is 1-2x106/kg CART-123 cells, preceded by lymphodepleting chemotherapy. The protocol-specified minimum acceptable dose for infusion is 1x105 CART cells/kg.

It is recommended per routine clinical care, that all subjects with marrow aplasia at Day 28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study, however subjects will continue to be followed on study. All subjects should therefore have a previously identified stem cell donor in order to participate in this study. Please see Section 6.8 for additional details.

All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion (Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Subjects With Refractory Acute Myeloid Leukemia
Actual Study Start Date : December 6, 2018
Estimated Primary Completion Date : December 3, 2021
Estimated Study Completion Date : December 3, 2033


Arm Intervention/treatment
Experimental: Treatment Arm
CART123 cells; cyclophosphamide; fludarabine
Biological: CART123 cells; cyclophosphamide; fludarabine

CART123 cells following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects will be treated with IV administration of CART123 cells using a split dosing approach (10% Day 0, 30% Day 1; 60% Day 2).

The total dose administered to each subject will be based on body weight obtained at the time of apheresis. Thus, the target total transduced dose is 1-2x10^6/kg CART123 cells, preceded by lymphodepleting chemotherapy. The protocol-specified minimum acceptable dose for infusion is 1x10^5 CART cells/kg.

Other Name: T Cells Containing Anti-CD123 Signaling Domains




Primary Outcome Measures :
  1. Safety profile of CART123 cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute (NCI) - Common Toxicity Criteria (v5.0) [ Time Frame: 5 years ]
    Assess the safety of CART123 cells in AML subjects following lymphodepletion with cyclophosphamide + fludarabine.

  2. Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility. [ Time Frame: 5 year ]
    Evaluate the percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility.


Secondary Outcome Measures :
  1. Estimation of CART123 efficacy by evaluation of OS and PFS of subjects at protocol defined intervals which receive at least one infusion of CART123 cells [ Time Frame: 15 years ]
    Estimate the efficacy of at least 1 dose of CART123 cells in AML subjects

  2. Overall Survival (OS) as percent of subjects surviving at protocol defined time points. [ Time Frame: 15 years ]
    Overall survival (OS) and progression-free survival (PFS)

  3. Progression-free survival (PFS) as percent of subjects surviving without disease progression at protocol defined time points [ Time Frame: 15 years ]
  4. Duration of response (DOR) [ Time Frame: 15 years ]
    Duration of response (DOR)

  5. Necessity of rescue bone marrow transplant [ Time Frame: 15 years ]
    Need for rescue allogeneic hematopoietic cell transplantation (alloHCT)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects 18 years of age or older
  2. Subjects with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. Specifically:

    1. AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria (Döhner et al., 2017 Blood, 129(4):424-447); partial remission or refractory disease (including primary refractory) are eligible. Or:
    2. AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible
  3. Subjects with relapsed disease after prior transplant must meet one of the following:

    a. Subjects with relapsed disease after prior allogeneic HCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and i. Have no residual donor cells (by STR analysis on 2 occasions separated by at least 1 month), OR: ii. Donor cells are present but there is no active GVHD (>Gr II), subject does not require systemic immunosuppression and is more than 3 months from transplant, and at least 1 month off GVHD prophylaxis.

    b. Subjects with relapsed disease after prior autologous or syngeneic HCT will be eligible if they meet all other inclusion criteria and it has been more than 3 months from transplant.

  4. Subjects must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
  5. Satisfactory organ functions:

    1. Creatinine ≤ 1.6 mg/dl
    2. ALT/AST must be ≤5 x upper limit of normal unless related to disease
    3. Direct bilirubin or total bilirubin < 2.0mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL);
    4. Left ventricular ejection fraction > 40% as confirmed by ECHO/MUGA
  6. ECOG Performance status 0-2.
  7. Written informed consent is given.
  8. No contraindications for leukapheresis.
  9. Subjects of reproductive potential must agree to use acceptable birth control methods (as described in protocol Section 4.3).

Exclusion Criteria:

  1. Pregnant or lactating (nursing women) women.
  2. Patients with relapsed AML with t(15:17).
  3. HIV infection.
  4. Active hepatitis B or hepatitis C infection.
  5. Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. For additional details regarding use of steroids while on study, please see Section 5.5.
  6. Any uncontrolled active medical disorder that would preclude participation as outlined.
  7. Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
  8. Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
  9. Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2).
  10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
  11. Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the Screening/Enrollment visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03766126


Contacts
Layout table for location contacts
Contact: EmergingMed 855-216-0098 PennCancerTrials@emergingmed.com

Locations
Layout table for location information
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: EmergingMed    855-216-0098    PennCancerTrials@emergingmed.com   
Contact: Saar Gill, MD, PhD       Saar.Gill@pennmedicine.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania

Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03766126     History of Changes
Other Study ID Numbers: 831619 (UPCC 35418)
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Pennsylvania:
refractory
relapsed
Acute
Myeloid
leukemia
AML

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites