Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

CD19.CAR-multiVSTs for Patients With CD19+ B-ALL or NHL Undergoing Related Allogeneic HSCT (CARMA)

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: NCT03768310
Recruitment Status : Not yet recruiting
First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Rayne Rouce, Baylor College of Medicine

Brief Summary:

This study is for patients that are having a bone marrow or stem cell transplant for either a type of cancer of the blood called Leukemia or a cancer of the lymph nodes called Non-Hodgkin's Lymphoma (NHL). Although a transplant can cure leukemia or lymphoma, some people will relapse (return of the disease). In those who relapse, current treatment cures only a very small percentage. This study is being conducted to evaluate the safety of a new type of therapy that may help to decrease the risk of relapse or treat relapse after it has occurred.

The body has different ways of fighting infection and disease. This study combines two of those ways, antibodies and T cells. Antibodies are proteins that protect the body from bacterial and other diseases. T cells are infection-fighting blood cells that can kill other cells, including tumor cells. 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.

The antibody used in this study is called anti-CD19. This antibody is attracted to cancer cells because of a substance on the outside of these cells called CD19. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor (also known as a CAR T cell). Although anti-CD19 antibodies or chimeric receptors can kill cancer cells, unfortunately they sometimes do not last long enough to destroy all of the cancer cells.

These CD19 chimeric receptor multivirus specific T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the biggest dose of chimeric T cells that is safe to administer, to determine what the side effects are, to see how long the T cells last and to evaluate whether this therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma having a bone marrow transplant.


Condition or disease Intervention/treatment Phase
Non-hodgkin Lymphoma Acute Lymphoblastic Leukemia Biological: CD19.CAR-multiVST for Group A Biological: CD19.CAR-multiVST for Group B Phase 1

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of the Administration of CD19 Chimeric Antigen Receptor Multivirus-Specific Cytotoxic T Lymphocytes for Prophylaxis or Therapy of Relapse of CD19 Positive Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2037


Arm Intervention/treatment
Experimental: CD19.CAR-multiVST for Group A

Group A: Patients with no evidence of disease after having a bone marrow transplant.

T cells will be given at the specified dose on or after day 30 after the bone marrow transplant. Three dose levels will be studied in both groups of patients (Group A and Group B). The lowest dose level will be 2 x 10^7cells/m2 and the highest will be 10 x10^7cells/m2.

Biological: CD19.CAR-multiVST for Group A
Patients will be evaluated in the clinic and a single dose of CD19.CAR-multiVSTs will be given by intravenous injection on or after 30 days of the transplant (between days 30 and 90). A time period of 6 weeks will constitute the time for clinical safety monitoring.
Other Name: CAR T Cells

Experimental: CD19.CAR-multiVST for Group B

Group B: Patients with evidence of disease before bone marrow transplant OR have relapsed after bone marrow transplant.

Patients in Group B will receive the T cells at the earliest feasible time point after the detection of disease, but no earlier than day 30 after the transplant. The three dose levels will be studied in both groups of patients (Group A and Group B). The lowest dose level will be 2 x 10^7cells/m2 and the highest will be 10 x10^7cells/m2.

Biological: CD19.CAR-multiVST for Group B
Patients will be evaluated in the clinic and a single dose of CD19.CAR-multiVSTs will be given by intravenous injection on or after 30 days of the bone marrow transplant. A time period of 6 weeks will constitute the time for clinical safety monitoring. If patients with relapse after transplant or those with evidence of disease before bone marrow transplant have at least a partial response to the treatment or have stable disease, they will be eligible to receive up to 6 additional doses of T cells separated by a minimum of four weeks. Patients are eligible to receive additional doses only after they have completed the initial 6-week clinical safety monitoring period.
Other Name: CAR T Cells




Primary Outcome Measures :
  1. Number of Patients with Dose-Limiting Toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: 6 weeks ]

    DLT will be defined as any of the following that is NOT (1) pre-existing, or (2) due to infection (for which patients with B-ALL, B-Lly, and B-NHL are predisposed), or (3) due to underlying malignancy, and that may, after consultation with the FDA when indicated, be considered possibly, probably, or definitely related to the study cellular products.

    • Any Grade 5 event
    • Non-hematologic DLT is any grade 3 or 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours
    • Grade 2 to 4 allergic reaction to T cell infusion
    • Hematologic DLT is defined as any Grade 4 hematologic toxicity that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days or within 28 days for patients with evidence of bone marrow disease
    • Acute GvHD grades III-IV within 42 days of the last T cell infusion


Secondary Outcome Measures :
  1. Overall response rate according to RECIST criteria. [ Time Frame: 4-8 weeks ]
    Overall response rate is defined as the proportion of subjects with best overall response of complete response (CR) or partial response (PR) according to RECIST criteria.



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

Inclusion Criteria:

  1. Diagnosis of CD19+ B-ALL or NHL undergoing related allogeneic HSCT, with no evidence of disease post-HSCT (Group A) OR minimal residual disease (MRD) at time of HSCT OR relapse post-HSCT (Group B).

    Morphologic relapse (for Group B) will be defined by accepted definitions in Section 5.6 of the full protocol, and measured by PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood.

    MRD will be defined as detection in blood or marrow of any of the following (at time of transplant or on post-transplant evaluation): a) Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient's leukemia cells pre-transplant on a post-transplant evaluation b) An immune globulin rearrangement known to be a disease marker for this patient c) A leukemia specific phenotype at a level of > 0.01%95, 96 d) Mixed donor chimerism.

  2. Age ≤ 75 years old
  3. Patients with life expectancy ≥ 12 weeks
  4. Patients with a Karnofsky/Lansky score ≥ 60
  5. Related Donor approved for stem cell transplant
  6. Patient or parent/guardian capable of providing informed consent
  7. Patients with bilirubin less than or equal to 2x upper limit of normal
  8. AST less than or equal to 3x upper limit of normal
  9. Creatinine ≤2x upper limit of normal for age
  10. Hemoglobin >7.0 (can be a transfused value)
  11. Pulse oximetry of >90% on room air
  12. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. The male partner should use a condom.
  13. Available stem cell donor-derived CD19-CAR transduced multi-virus-specific cytotoxic T lymphocytes with 15% expression of CD19-CAR determined by flow-cytometry and <10% cytotoxicity against patient or donor-derived (or other family member-derived) PHA blasts.

Exclusion Criteria:

  1. Severe intercurrent infection: Patients with a concurrent bacterial infection must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  2. Evidence of graft versus host disease >grade II
  3. Pregnant or lactating
  4. History of hypersensitivity reactions to murine protein-containing products.
  5. Currently taking corticosteroids for therapy of GVHD at a dose of >0.5mg/kg prednisone equivalent.
  6. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 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.
  7. Patients who have received donor lymphocyte infusion (DLI) within 28 days.

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): NCT03768310


Contacts
Layout table for location contacts
Contact: Rayne H Rouce, MD 832-824-4716 rouce@bcm.edu
Contact: Jacqueline Castello 832-824-4391 jxcastel@texaschildrens.org

Locations
Layout table for location information
United States, Texas
Houston Methodist Hosptial Not yet recruiting
Houston, Texas, United States, 77030
Contact: Rayne H Rouce, MD    832-824-4716    rouce@bcm.edu   
Contact: Jacqueline Castello    832-824-4391    Jacqueline.Castello@bcm.edu   
Texas Children's Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Rayne H Rouce, MD    832-824-4716    rouce@bcm.edu   
Contact: Jacqueline Castello    832-824-4391    jxcastel@texaschildrens.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Rayne H Rouce, MD Baylor College of Medicine

Layout table for additonal information
Responsible Party: Rayne Rouce, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03768310     History of Changes
Other Study ID Numbers: H-36578 CARMA
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

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 Rayne Rouce, Baylor College of Medicine:
ALL
NHL
hematopoietic stem cell transplantation (HSCT)

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia