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Trial record 29 of 256 for:    "methodist hospital" | Recruiting, Not yet recruiting, Available Studies | Houston

Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (MAGENTA)

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ClinicalTrials.gov Identifier: NCT03081910
Recruitment Status : Recruiting
First Posted : March 16, 2017
Last Update Posted : March 15, 2019
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Information provided by (Responsible Party):
Rayne Rouce, Baylor College of Medicine

Brief Summary:

Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer).

The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients.

T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD5. It first came from mice that have developed immunity to human leukemia. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5. CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD5 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.

In the laboratory, the investigators have also found that T cells work better if proteins that stimulate T cells are also added, such as one called CD28. Adding the CD28 makes the cells grow better and last longer in the body, thus giving the cells a better chance of killing the leukemia or lymphoma cells.

In this study investigators are going to attach the CD5 chimeric receptor with CD28 added to it to the patient's T cells. The investigators will then test how long the cells last. These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration .


Condition or disease Intervention/treatment Phase
T-cell Acute Lymphoblastic Lymphoma T-non-Hodgkin Lymphoma T-cell Acute Lymphoblastic Leukemia Genetic: CD5.CAR/28zeta CAR T cells Drug: Fludarabine Drug: Cytoxan Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Therapy of Manufactured Autologous T-Cells Expressing a Second Generation Chimeric Antigen Receptor (CAR) for Treatment of T-Cell Malignancies Expressing CD5 Antigen
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : June 1, 2036


Arm Intervention/treatment
Experimental: CD5.CAR/28zeta CAR T cells
Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.If patients have experienced either a partial response or stable disease and completed the 6 week toxicity evalution without evidence of DLT or other infectious complications, they will be eligible to receive up to 3 additional infusions of CD5 CAR.T cells. Patients remain eligible for up to 3 additional infusions as long as they continue to have a clinical response and absence of safety concerns. If patients experience a complete response following an additional infusion, investigators will recommend they proceed to allogeneic HSCT.
Genetic: CD5.CAR/28zeta CAR T cells

Three dose levels will be evaluated:

Dose level one: 1×10^7 cells/m2

Dose level two: 5×10^7 cells/m2

Dose level three: 1×10^8 cells/m2

The first six (6) patients treated on the study will be adults (>18 yrs of age). Six adolescents (age 12-18) will be treated before children (>3 yrs of age) are eligible.

Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.


Drug: Fludarabine
Patients will receive 3 daily doses of fludarabine (30 mg/m2) to induce lymphopenia, finishing at least 24 hours before T cell infusion. Infusions should be given following hospital/pharmacy recommendations (including dose adjustments as appropriate per institutional guidelines) however at a minimum the fludarabine should be infused over 30 minutes. Mesna, IV hydration and anti-emetics should also be provided following local institutional guidelines.
Other Name: Fludara

Drug: Cytoxan
Patients will receive 3 daily doses of cyclophosphamide (500 mg/m2/day) to induce lymphopenia, finishing at least 24 hours before T cell infusion. Infusions should be given following hospital/pharmacy recommendations (including dose adjustments as appropriate per institutional guidelines) however at a minimum the cyclophosphamide should be infused over 1 hour. Mesna, IV hydration and anti-emetics should also be provided following local institutional guidelines.
Other Name: cyclophosphamide




Primary Outcome Measures :
  1. Number of Patients with dose limiting toxicity [ Time Frame: 6 weeks ]
    To evaluate the safety of escalating doses of autologous peripheral blood T lymphocytes (ATLs) genetically modified to express chimeric antigen receptors (CAR) targeting the CD5 molecule (CD5.CAR) in combination with lymphodepletion in patients with relapsed/refractory T-cell malignancies.


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 6 weeks ]
    To measure the anti-tumor effects of CD5.CAR-ATLs in patients with T-cell leukemia or lymphoma.



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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Procurement Inclusion Criteria

Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:

  1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher)

    AND Suitable for allogeneic HSCT with confirmation of an identified eligible allo-HSCT donor by a FACT accredited transplant center

    AND with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.

  2. CD5-positive tumor (result can be pending at this time). > 50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory.
  3. Age less than or equal to 75 years old. NOTE: The first six (6) patients treated on the study will be adults (>18 yrs of age). Six adolescents (age 12-18) will be treated before children (>3 yrs of age) are eligible.
  4. Hgb greater than or equal to 7.0 (can be transfused)
  5. Life expectancy greater than 12 weeks
  6. If pheresis required to collect blood:

    • Creatinine <1.5 × upper limit normal
    • AST <1.5 × upper limit normal
    • PT and APTT <1.5 × upper limit normal
  7. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Procurement Exclusion Criteria:

  1. Active infection requiring antibiotics.
  2. Active infection with HIV or HTLV.
  3. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
  4. Cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF less than or equal to 30% or LVEF less than or equal to 50% or clinically significant pericardial effusion; Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions within 12 months of treatment).
  5. History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.

Treatment Inclusion Criteria:

  1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher)

    AND suitable for allogeneic HSCT with confirmation of an identified eligible allo-HSCT donor by a FACT accredited transplant center

    AND with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.

  2. CD5-positive tumor: >50% CD5+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified Flow Cytometry/Pathology laboratory.
  3. Age less than or equal to 75 years old. NOTE: The first six (6) patients treated on the study will be adults (>18 yrs of age). Six adolescents (age 12-18) will be treated before children (>3 yrs of age) are eligible.
  4. Bilirubin less than 3 times the upper limit of normal.
  5. AST less than 5 times the upper limit of normal.
  6. Estimated GFR > 60 mL/min.
  7. Pulse oximetry of > 90% on room air
  8. Karnofsky or Lansky score of greater than or equal to 60%.
  9. Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study.
  10. Available autologous activated peripheral blood T cell products with greater than or equal to 20% expression of CD5.CAR.28 zeta and <0.5% gene-modified malignant T blasts by flow cytometry.
  11. Life expectancy of greater than 12 weeks.
  12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
  13. Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Exclusion Criteria:

  1. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.
  2. History of hypersensitivity reactions to murine protein-containing products.
  3. Pregnant or lactating.
  4. Tumor in a location where enlargement could cause airway obstruction.
  5. Active infection with HIV or HTLV.
  6. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
  7. Cardiac criteria: Prolonged QT syndrome; Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Cardiac echocardiography with LVSF less than or equal to 30% or LVEF less than or equal to 50%; Cardiac dysfunction NYHA III or IV; Cardiac echocardiography with clinically significant pericardial effusion.
  8. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with greater than or equal to 5 WBCs per mm3; History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

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): NCT03081910


Contacts
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Contact: Rayne Rouce, MD 832-824-4716 rhrouce@txch.org
Contact: Josalind Randall 832-824-6835 jxrandal@txch.org

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Rayne Rouce, MD    832-824-4716    rhrouce@txch.org   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Rayne Rouce, MD    832-824-4716    rhrouce@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Investigators
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Principal Investigator: Rayne Rouce, MD Baylor College of Medicine

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Responsible Party: Rayne Rouce, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03081910     History of Changes
Other Study ID Numbers: H-40466, MAGENTA
First Posted: March 16, 2017    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Rayne Rouce, Baylor College of Medicine:
Autologous CAR T cells
T-cell acute lymphoblastic lymphoma
T-non-Hodgkin Lymphoma
T-cell Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Vidarabine
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
Antiviral Agents
Anti-Infective Agents