Trial Title:
Chimeric Antigen Receptor Treatment Targeting CD70 (SEVENTY)
NCT ID:
NCT06345027
Condition:
Leukemia, Myeloid, Acute
Leukemia, B-cell
Leukemia, T-Cell
Lymphoma
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, B-Cell
Leukemia, T-Cell
Conditions: Keywords:
Leukemia
Lymphoma
Acute myeloid
B cell
T cell
Blood cancer
Lymph gland cancer
CD70.CAR T-cells
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Treatment Arm A
Description:
Each patient will receive one T cell infusion.
CD70.CAR Dose Levels / Cell Dose (transduced cells):
Dose Level -1: 3 x 10^5 cells/kg Dose Level 1 (starting dose level): 1 x 10^6 cells/kg
Dose Level 2: 3 x 10^6 cells/kg Dose Level 3: 1 x 10^7 cells/kg
*First three patients treated on the study will be adults 18 years of age or older.
Arm group label:
Treatment Arm A
Summary:
This study is for patients that have lymph gland disease called Hodgkin or non-Hodgkin
Lymphoma or T/NK-lymphoproliferative disease and the patients condition has come back or
has not gone away after treatment, including the best treatment we know for these
diseases.
Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that
is sometimes called Epstein Barr virus (EBV). This virus causes mononucleosis or
glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the
cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma. This
suggests that the EBV plays a role in causing Lymphoma. The cancer cells (in lymphoma)
and some immune system cells infected by EBV are able to hide from the body's immune
system and escape destruction.
T cells, also called T lymphocytes, are special infection-fighting blood cells that can
kill other cells, including cells infected with viruses and tumor cells. T cells have
been used to treat patients with cancers. T cells, that have been trained to kill EBV
infected cells can survive in blood and affect the tumor. We have treated over 80 people
on studies using T cells to target these diseases. About half of those patients who had
disease at the time they got the cells had responses including some patients with
complete responses (meaning the cancer could no longer be detected).
We think that if T cells are able to last longer in the body, they may have a better
chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add
a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know
that T cells need substances called cytokines (substances such as proteins released by
specific cells of the immune system) to survive and that the cells may not get enough
cytokines after the cells are infused into the body. We have added the gene C7R that
gives the cells a constant supply of cytokine and helps them to survive for a longer
period of time.
The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and
additionally to evaluate how long they can be detected in the blood and what affect they
have on the cancer.
Detailed description:
Patients will be enrolled to this study in two treatment groups: C7R-EBVSTs without
lymphodepletion (Group A) and C7R-EBVSTs with lymphodepletion (Group B). The
investigators will enroll patients into group B if limited expansion and clinical
effectiveness is seen in Group A.
Patients will give blood to make C7R EBV T cells. These cells will be kept frozen until
they are given to the patient.
The lines are made using a special process. To make the VSTs donor cells are mixed with
small pieces of proteins, called peptides that are identical to proteins from EBV. First
unwanted cells are separated from the donor blood. The unwanted cells have CD45RA on
their surface and can be identified and removed from the product leaving behind only the
T cells that contain a small number of VSTs. The cells are then stimulated with the
peptides to make them grow. After about 9 days the growth of the VSTs starts to slow down
and they are stimulated a second time (and possibly a third) with peptides together with
cells from the donor that have been modified to help train the T cells to kill cells that
are infected with EBV as well as a cell line (called ULCL) that helps the T-cells to
grow. ULCL is made by infecting lymphocytes with EBV that has been made non-infectious by
deleting a part of its DNA. ULCL is irradiated before use so that it cannot grow. Once
enough VSTs are made they are frozen and tested to make sure they can recognize virus
infected cells but not normal cells.
To get the C7R to be made by the T-cell, a gene is inserted into the T-cell. This is done
using certain parts of a virus (known as a retrovirus). A retrovirus is a type of virus
that inserts a copy of its own genetic material into the DNA of a different host cell.
The retrovirus can carry the gene into the T cells. Patients that have received cells
with a new gene in them will be followed for a total of 15 years in order to see if there
are any long term side effects of gene transfer. Gene transfer is the insertion of
genetic material into a cell.
Patients that enroll on this study will be assigned a dose of C7 R EBV T cells. The
assigned dose of cells is based on body weight and height. In Group A, in this study
patients will receive the C7 R EBV T cells. If in Group B, along with the C7R EBV T
cells, patients will and may also receive cyclophosphamide and fludarabine. These two
drugs are standard chemotherapy medicines and may be given before the T cells to make
space in the blood for the T cells to grow after the patient has received them.
If in Group B, patients may receive cyclophosphamide and fludarabine, these drugs will be
given intravenously (through an i.v. needle inserted in the vein or the central line) for
2 days and then fludarabine alone on the third day (Day -4, -3, -2) before the infusion.
On Day 0, patients will be given an injection of C7 R EBV T cells into the vein through
an IV line at the assigned dose.
Before receiving the T cell infusion, patients may be given a dose of Benadryl
(diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 and 10
minutes. Patients will be monitored in the clinic or hospital for about 2 hours. The
treatment will be given by the Center for Cell and Gene Therapy at Texas Children's
Hospital or Houston Methodist Hospital. Patients should plan to stay in Houston for at
least 2 weeks after the infusion to be monitored for side effects.
Patients will have follow-up visits with the clinic after the infusion (at scheduled
visits weeks 2 and 6, and nursing follow up at weeks 1, 2, 4 and 6 after the infusion,
and at months 3, 6, 9, and 12 after the infusion. The patients will also have nursing
follow up annually for the next 15 years, and scheduled disease evaluations after the
T-cell injection (at week 6 +/- 2 weeks after the infusion and then as clinically
needed).
After disease re-evaluation, if the disease has not gotten worse, or if in the future it
seems that patients might benefit and have not had a severe side effect caused by the
infusion of the C7R EBV T cells, the patients may be eligible to receive one additional
dose of the T cells. The dose will be at the same dose level as the first infusion and
separated by at least 4 weeks to make sure there are no severe side effects between
infusions. Patients that receive an additional dose of C7R EBV T-cells, should plan to
stay in Houston for at least 2 weeks after the infusion to be monitored for side effects.
Medical tests before treatment--
Before being treated, patients receive a series of standard medical tests:
1. Physical exam
2. Blood tests to measure blood cells, kidney and liver function
3. Measurements of the tumor by routine imaging studies. Imaging studies that have been
used in the past will be used to best assess the tumor (Computer Tomogram (CT) or
Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT) and/or
Bone Scan).
Medical tests during and after treatment--
Patients will receive standard medical tests while receiving the infusions and
afterwards:
1. Physical exams
2. Blood tests to measure blood cells, kidney and liver function
3. Measurements of the tumor by routine imaging studies approximately 6 weeks after the
infusion.
4. Tumor biopsy of an accessible tumor between 2-4 weeks after the infusion and as
clinically indicated thereafter.
To learn more about the way the C7R EBV T cells are working and how long they last in the
body, an extra amount of blood will be obtained on the day that chemotherapy starts, on
the day of the T-cell infusion(s) and at the end of the T-cell infusion(s). Blood will
also be obtained at 1, 2, 4, 6 weeks after the T-cell infusion(s) and every 3 months for
the 1st year. Blood will then be obtained annually for the next 15 years and possibly at
additional time points. The amount of blood taken will be based on weight with up to a
maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For children,
the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon) per 2
lbs (1 kg) of body weight on any one day. This volume is considered safe, but may be
decreased if the patient is anemic (have a low red blood cell count).
Criteria for eligibility:
Criteria:
Procurement Inclusion Criteria:
1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the
exception of acute promyelocytic leukemia (APL). Patients with targetable mutations
should have failed or be ineligible for targeted therapies (e.g. FLT3 inhibitors,
IDH inhibitors or anti-CD33 drug conjugate)
OR
Patients with other relapsed or refractory CD70+ hematological malignancies that
would be considered an indication for allogeneic Hematopoietic Stem Cell Transplant
(HSCT) if remission can be achieved. (Patients with CD19+ malignancies only: must
have failed or be ineligible to receive commercial CD19.CAR T cell treatments.)
Primary refractory or resistant disease, defined as not achieving complete remission
(CR) (i.e., a remaining blast count of 5% or more) after 1 to 2 cycles of intense
induction therapy.
Relapse is defined as (1) hematologic relapse after complete remission based on bone
marrow blasts >=5%, or reappearance of blasts in the blood, or development of
extramedullary disease; (2) molecular relapse after minimal residual disease (MRD)
negative, complete remission based on reoccurrence of MRD as assessed by RT-qPCR or
by multi-parametric flow cytometry (MFC)
2. CD70 positive tumor with at least 30% CD70+ blasts by flow cytometry or
immunohistochemistry (staining can be pending at time of procurement)
3. Age ≤75 years. NOTE: The first three (3) patients treated on the study will be
adults (≥18 years of age)
4. Hemoglobin ≥ 7.0 g/dL (can be transfused)
5. If apheresis required to collect blood
- PT and aPTT <1.5x ULN
- Serum Creatinine < 2 x ULN
- AST < 5 x ULN
6. Informed consent
Procurement Exclusion Criteria:
1. Diagnosis of acute promyelocytic leukemia (APL)
2. Active infection (bacterial, fungal, or viral) requiring ongoing treatment without
improvement.
3. Known active infection with HIV or HTLV (collected blood will be sent for HIV/HTLV
testing, separate testing prior to procurement not required)
4. Active second cancer (except non-melanoma skin cancer or in situ breast cancer or
cervical cancer) or other cancer treated ≤ 2 years prior to enrollment
5. Ongoing treatment with immune suppression for prophylaxis/treatment of GVHD
including high dose steroids (e.g. prednisone equivalent > 0.5 mg/kg/day)
Treatment Inclusion Criteria:
1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the
exception of acute promyelocytic leukemia (APL) Patients with targetable mutations
should have failed or be ineligible for targeted therapies (e.g. FLT3 inhibitors,
IDH inhibitors, or anti-CD33 drug conjugate).
OR
Patients with other relapsed or refractory CD70+ hematological malignancies that
would be considered an indication for allogeneic Hematopoietic Stem Cell Transplant
(HSCT) if remission can be achieved. Patients with CD19+ malignancies only: must
have failed or be ineligible to receive commercial CD19.CAR T cell treatments.
Primary refractory or resistant disease as defined by not achieving complete
remission (CR) (i.e., a remaining blast count of 5% or more) after 1 to 2 cycles of
intense induction therapy.
Relapse is defined as (1) hematologic relapse after complete remission based on bone
marrow blasts >=5%, or reappearance of blasts in the blood, or development of
extramedullary disease; (2) molecular relapse after minimal residual disease (MRD)
negative, complete remission based on reoccurrence of MRD as assessed by RT-qPCR or
by multi-parametric flow cytometry (MFC)
2. Confirmation from the patient's primary physician team of a suitable allogeneic
hematopoietic stem cell transplant (HSCT) donor. OR Documentation that patient
declines a potential subsequent HSCT)
3. CD70 positive tumor with at least 30% CD70+ blasts by flow cytometry or
immunohistochemistry (tissue)
4. No systemic chemotherapy at least 2 weeks prior to treatment on study and must be
recovered from all acute toxic effects of prior chemotherapy at time of treatment.
5. Age ≤ 75 years. NOTE: The first three (3) patients treated on the study should be
adults (≥18 years of age). Thereafter, a thorough review of the safety data will be
performed and submitted to the FDA for approval prior to enrolling pediatric
patients.
6. Hemoglobin ≥ 7.0 g/dL (can be transfused)
7. Total bilirubin < 3 times the upper limit of normal
8. AST/ALT < 5 times the upper limit of normal
9. Estimated GFR ≥ 60ml/min
10. Pulse oximetry of > 90% on room air
11. Karnofsky/Lansky score of ≥ 60%
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. Male
partner should use a condom
13. Informed consent obtained
Treatment Exclusion Criteria:
1. Diagnosis of acute promyelocytic leukemia (APL)
2. Currently receiving any investigational agents or received any tumor vaccines within
the previous 6 weeks.
3. Pregnant or lactating.
4. Active infection with HIV or HTLV
5. Clinically significant bacterial, fungal, or viral infection requiring ongoing
therapy without improvement.
6. Cardiac criteria: Cardiac echocardiography with LVEF<50%; Cardiac dysfunction NYHA
III or IV; Clinically significant pericardial effusion. Confirmation of absence of
these conditions within 6 months of treatment.
7. CNS abnormalities: Presence of CNS disease defined as detectable cerebrospinal blast
cells in a sample of CSF with ≥ 5 WBCs per mm3 or known CNS tumors/chloromas
8. Use of serotherapy with Campath or Anti-Thymocyte Globulin (ATG) within the last 28
days
9. Use of Donor Lymphocyte Infusion (DLI) or other cellular therapy product within 28
days
10. Acute GVHD ≥ Grade 2 or moderate to severe (formerly extensive) chronic GVHD
11. High dose steroids >1 mg/kg within preceding 5 days or currently receiving
>0.5mg/kg/day prednisone equivalent
12. Hyperleukocytosis (WBC ≥ 50K) or rapidly progressive disease that in the estimation
of the investigator would compromise the ability of the patient to complete the
study within 3 months of allogeneic HSCT
Gender:
All
Minimum age:
N/A
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Texas Children's Hospital
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Bilal Omer, MD
Phone:
832-826-0860
Email:
baomer@texaschildrens.org
Facility:
Name:
The Methodist Hospital
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Bilal Omer, MD
Phone:
832-826-0860
Email:
baomer@texaschildrens.org
Start date:
December 1, 2024
Completion date:
April 1, 2042
Lead sponsor:
Agency:
Baylor College of Medicine
Agency class:
Other
Source:
Baylor College of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06345027
