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

NCT03768310 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: H-36578 CARMA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-hodgkin Lymphoma; Acute Lymphoblastic Leukemia

Keywords

ALL; NHL; hematopoietic stem cell transplantation (HSCT)

Outcome Measures

Primary Outcomes (1)

• Number of Patients with Dose-Limiting Toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  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

  6 weeks

Secondary Outcomes (1)

• Overall response rate according to RECIST criteria.

  4-8 weeks

Study Arms (2)

CD19.CAR-multiVST for Group A

EXPERIMENTAL

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

CD19.CAR-multiVST for Group B

EXPERIMENTAL

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

Interventions

CD19.CAR-multiVST for Group A BIOLOGICAL

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.

Also known as: CAR T Cells

CD19.CAR-multiVST for Group A

CD19.CAR-multiVST for Group B BIOLOGICAL

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.

Also known as: CAR T Cells

CD19.CAR-multiVST for Group B

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≤ 75 years old
• Patients with life expectancy ≥ 12 weeks
• Patients with a Karnofsky/Lansky score ≥ 60
• Related Donor approved for stem cell transplant
• Patient or parent/guardian capable of providing informed consent
• Patients with bilirubin less than or equal to 2x upper limit of normal
• AST less than or equal to 3x upper limit of normal
• Creatinine ≤2x upper limit of normal for age
• Hemoglobin \>7.0 (can be a transfused value)
• Pulse oximetry of \>90% on room air
• 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.
• 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.

You may not qualify if:

• 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.
• Evidence of graft versus host disease \>grade II
• Pregnant or lactating
• History of hypersensitivity reactions to murine protein-containing products.
• Currently taking corticosteroids for therapy of GVHD at a dose of \>0.5mg/kg prednisone equivalent.
• 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.
• Patients who have received donor lymphocyte infusion (DLI) within 28 days.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hosptial

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Rayne H Rouce, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: December 7, 2018
• Study Start: June 1, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2040
• Last Updated: July 21, 2022

Record last verified: 2022-07

Locations

US (2)