Lymphoma Clinical Trial
Official title:
A Phase I/IIa, Open-label, Non-randomized, Study of ASC-101 in Patients With Hematologic Malignancies or Myelodysplastic Syndrome (MDS) Who Are Candidates for Dual-cord Umbilical Cord Blood Transplantation (UCBT)
The goal of this clinical research study is to learn if it is safe and feasible to transplant
patients with one of two units of cord blood that has been changed in the laboratory before
it is given. Only patients with leukemia, lymphoma or myelodysplastic syndrome will be
allowed on this study. The secondary goal is to obtain the preliminary efficacy outcome.
Researchers also want to learn if using cord blood that has been changed can help to control
the disease.
One cord blood unit will not be changed before it is administered to you. The cord blood unit
that will be altered will be changed to use sugar that is found in small amounts in blood
cells. It plays a role in telling transplanted cells where they should go in the body. Adding
more sugars to the cord blood cells in the laboratory helps the cord blood cells find their
way to the bone marrow faster. This process is called fucosylation.
"Conditioning" is the chemo and other medicines and will be given to patients to prepare to
receive cord blood transplant cells. This prevents immune system from rejecting the cells.
Conditioning will be started before the transplant.
ATG is a protein that removes immune cells that cause damage to the body.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer
cells to die. This chemotherapy is also designed to block your body's ability to reject the
donor's bone marrow cells.
Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells
to die.
MMF and tacrolimus are designed to block the donor cells from growing and spreading in a way
that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue
attacks the recipient's body). This may help to prevent GVHD.
Rituximab is designed to attach to cancer cells, which may cause them to die.
A Phase I study for treatment of patients (N=25) with hematologic malignancies and MDS who
are candidates for dual-cord UCBT is ongoing at M.D. Anderson Cancer Center under an
Investigator-initiated IND Application, E.J. Shpall, MD, PI. Since August, 2012, Preliminary
results indicate that ASC-101 UCBT is well-tolerated and no ASC-101 related untoward adverse
events have been observed. To date, the median time to neutrophil engraftment (N=9) is 15
days, and the median time to platelet engraftment (N=9) is 33 days. The trial remains
ongoing.
Central Venous Catheter Placement:
You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube
that will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form for it.
The chemotherapy, some of the other drugs in this study, and the cord blood transplant will
be given by vein through your CVC. Blood samples will also be drawn through your CVC. The CVC
will remain in your body for about 2-5 months.
Study Plans:
If you agree to take part in this study, your doctor will choose one of the following 2 study
plans based on the disease and your age and medical history.
Fludarabine/Clofarabine/Busulfan/Rituximab/Total Body Irradiation:
If you are between 1 and 80 years of age and can receive high-dose chemotherapy, and your
doctor agrees, you will receive fludarabine, clofarabine, busulfan, ATG, total body
irradiation, and possibly rituximab.
If you are receiving this study plan medication, blood may be drawn to check levels of
busulfan 1 or more times over the 4-day course of treatment. No more than 1 teaspoon will be
taken at each blood draw.
Day Treatment
- Day0 Admit, IV hydration, rituximab 375 mg/m2 (B cell malignancy)
- Day1 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day2 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day3 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000
- Day4 Fludarabine 10 mg/m2, clofarabine 30 mg/m2, busulfan AUC 5,000, rabbit ATG 1.25
mg/kg
- Day5 Low-dose TBI 2 Gy in AM, rabbit ATG 1.75 mg/kg
- Day6 Rest
- Day7 Rest
- Day8 Cord blood infusions
Fludarabine, Melphalan
Day Treatment
- Day0 Admit, hydration
- Day1 Fludarabine 40 mg/m2 IV
- Day2 Fludarabine 40 mg/m2 IV, rabbit ATG 1.25 mg/kg
- Day3 Fludarabine 40 mg/m2 IV, rabbit ATG 1.75 mg/kg
- Day4 Fludarabine 40 mg/m2 IV and Melphalan 140 mg/m2 IV
- Day5 Rest
- Day6 Cord blood infusions
Supportive Drugs:
Starting on Day -3, you will receive mycophenolate mofetil as a tablet by mouth 2 times a
day. If you are not able to take the tablet by mouth, you will receive MMF by vein over 2
hours 2 times a day. If you do not have GVHD at Day 100 after your cord blood transplant, the
dose of MMF will be gradually lowered. If you have GVHD, MMF may be stopped 7 days after the
GVHD is controlled.
Starting on Day -2, you will receive tacrolimus by vein as a continuous (nonstop) infusion
until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day
for about 6 months. After that, your tacrolimus dose may be gradually lowered if you do not
have GVHD. Your doctor will discuss this with you.
Starting on Day 0, you will receive filgrastim (G-CSF) through a needle under the skin 1 time
a day every day until your white blood count begins to recover. Filgrastim is designed to
help cells in the bone marrow to divide, which helps raise white blood cells counts more
quickly, lower fever, and decrease the risk of infection.
Study Visits:
At about 6 weeks, 3, 6, and 12 months after the transplant:
- You will have a physical exam.
- You will be checked for possible reactions to the transplant and study drugs, including
GVHD.
- Blood (about 4 teaspoons) will be drawn for routine tests, to check for CMV antibodies,
and for genetic tests to learn if the donor's cells have "taken". The routine blood
tests will be repeated as often as the doctor thinks is needed.
- If the doctor thinks it is needed, you will have a bone marrow aspiration to check the
status of the disease.
You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you
will continue as an outpatient in the hospital area, which means you will have to stay close
enough to be able to come back for any visits for about 100 days after the transplant.
Length of Participation:
If the study suits you and you agree to join, you will be in it for one year after your
transplant. You will be taken off study early if the disease gets worse, if intolerable side
effects occur, if the cord blood is infected and cannot be transplanted, if you are unable to
follow study directions, or if your doctor thinks it is in your best interest.
This is an investigational study. Fucosylation is not an FDA-approved process. It is
currently being used for research purposes only. Fludarabine, busulfan, clofarabine,
melphalan, mycophenolate mofetil, tacrolimus, and rituximab are FDA approved and commercially
available to be given to patients with leukemia or lymphoma having a cord blood transplant.
Total body irradiation is delivered using FDA-approved and commercially available methods.
Up to 25 patients will be enrolled in this study. All will be enrolled at M.D. Anderson
Cancer Center, Scripps Green Hospital,University Hospitals Case Medical Center, and Texas
Transplant Institute.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05540340 -
A Study of Melphalan in People With Lymphoma Getting an Autologous Hematopoietic Cell Transplant
|
Phase 1 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Completed |
NCT00001512 -
Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Completed |
NCT01410630 -
FLT-PET/CT vs FDG-PET/CT for Therapy Monitoring of Diffuse Large B-cell Lymphoma
|
||
Active, not recruiting |
NCT04270266 -
Mind-Body Medicine for the Improvement of Quality of Life in Adolescents and Young Adults Coping With Lymphoma
|
N/A | |
Terminated |
NCT00801931 -
Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders
|
Phase 1/Phase 2 | |
Completed |
NCT01949883 -
A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma
|
Phase 1 | |
Completed |
NCT01682226 -
Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
Recruiting |
NCT05019976 -
Radiation Dose Study for Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma
|
N/A | |
Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
Completed |
NCT04434937 -
Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213)
|
Phase 2 | |
Completed |
NCT01855750 -
A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
|
Phase 3 | |
Terminated |
NCT00788125 -
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
|
Phase 1/Phase 2 | |
Terminated |
NCT00775268 -
18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Terminated |
NCT00014560 -
Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Recruiting |
NCT04977024 -
SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer
|
Phase 2 | |
Active, not recruiting |
NCT03936465 -
Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer
|
Phase 1 |