LymphomaPhase 2NCT00536978
Natural Killer (NK) Cell Adback After Allogeneic Stem Cell Transplant With Campath-IH Plus Chemorx for Patients With Lymphoid Malignancies
A Phase 2 study testing ARA-C, BCNU and Campath-1H in people with Lymphoma and Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary objective: To determine the safety of adback T- or Natural Killer (NK) cells in patients with lymphoid malignancies receiving allogeneic stem cell transplantation with Campath-IH containing conditioning regimen. Secondary objective: To determine the efficacy (disease-free-survival) of this strategy. Read more about this study
- Who is it for?
- Ages Up to 70 years
- What is being tested?
- ARA-C, BCNU and Campath-1H
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Nov 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Up to 70 years of age.
- B-cell lymphoid malignancies (those with CD20 negative disease at their diagnosis will not receive rituximab): This includes CLL/small lymphocytic lymphoma, follicular lymphoma, mantle cell, diffuse large cell, Splenic lymphoma, Mucosa-Associated Lymphoid Tissue (MALT), lymphoplasmacytic lymphoma and Burkitt's lymphoma.
- Patients in relapse or considered at high risk for relapse.
- In order to increase the chance of KIR-mismatching between recipient and donor, a 9/10 matched (mismatched locus C ) unrelated donor would be preferable. If a mismatched donor is not available, then a fully-matched unrelated donor or other 9/10 matched unrelated donor will be considered.
- A sibling donor who is 9/10 matched may also be allowed.
- Zubrod PS </= 2.
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- Left ventricular ejection fraction (LVEF)>/= 40% with no uncontrolled arrythmias or symptomatic heart disease.
- Forced expiratory volume in one second (FEV1), Forced Expiratory Volume (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) >/= 50%.
- Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3 * upper limit of normal,
- Aspartate aminotransferase (AST) < 3 * upper limit of normal.
- Signed, written Internal Review Board (IRB)-approved informed consent.
- Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
Who cannot join
- Past history of anaphylaxis following exposure to CAMPATH-IH or Rituximab
- Patient with active Central Nervous System (CNS) disease.
- Positive Beta human chorionic gonadotrophin (hCG) text in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization, or currently breast-feeding.
- Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
- Patients with other malignancies diagnosed within 2 years prior to Study registration (except skin squamous cell carcinoma).
- Active uncontrolled bacterial, viral or fungal infections.
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- Major surgical procedure or significant traumatic injury within 4 weeks prior to Study registration.
- Serious, non-healing wound, ulcer, or bone fracture.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Study registration.
- History of Stroke within 6 months.
- Myocardial infarction within the past 6 months prior to Study registration.
- Uncontrolled chronic diarrhea.
- A prior allogeneic transplant from the same donor. Is there an age limit? Yes
Trial locations and contacts
1 site in 1 country.
About this study
Official title: T-Cell or Natural Killer (NK) Cell Adback in Patients With Lymphoid Malignancies Receiving Allogeneic Stem Cell Transplantation With Campath-IH Containing Conditioning Regimens
Primary objective:
- To determine the safety of adback T- or Natural Killer (NK) cells in patients with lymphoid malignancies receiving allogeneic stem cell transplantation with Campath-IH containing conditioning regimen.
Secondary objective:
- To determine the efficacy (disease-free-survival) of this strategy.
Read the detailed description
NK Cells, T-Cells, and the Study Drugs:
NK and T-cells from a donor may decrease the risk of relapse (reappearance of disease) after stem cell transplantation. NK cells and T-cells are kinds of white blood cells. Both types of cells have the ability to fight infection and "kill" tumor cells in the body. NK cells are called "natural killers" because, unlike T-cells, NK cells do not need to be activated ("turned on") by an antigen (a foreign substance) in order to "attack" and "kill" tumor cells.
Screening Tests:
Before starting treatment on this study, "screening tests" will be performed to help the doctor determine eligibility to take part in this study.
- Physical exam.
- Blood drawn (about 6 1/2 to 8 tablespoons) for routine tests, to check the effects of the transplantation, and for a liver function test. This routine blood draw will also include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
- Urine collected for routine tests.
- Bone marrow biopsy performed to check the status of the disease. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Chest x-ray, computed tomography (CT) scans, and an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).
Study Treatment:
Treatment will begin within 30 days after the screening visit. All of the study drugs will be given through a central venous catheter (CVC) that will be left in place throughout treatment. 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 in more detail, and a signed separate consent form for this procedure is required
Before starting the chemotherapy in this study, 21 or more days must have elapsed since the last biological therapy, chemotherapy, radiotherapy, or other investigational therapy.
PATIENTS RECEIVING BEAM, CAMPATH-IH, AND RITUXIMAB AS CONDITIONING:
BEAM is designed to kill leukemia and lymphoma cells by inserting itself into the cell DNA (genetic material of cells).
Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain immune cells, which may cause the cells to die.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
On Day 1, BCNU will be given over 1 hour.
On Days 2-5, Ara-C will be given over 1 hour and etoposide over 3 hours. This will be repeated every 12 hours during these 4 days.
On Days 2-4, alemtuzumab will be given over 30 minutes. Hydrocortisone and tacrolimus will be given by vein during this time to help prevent or ease side effects, such as chills, skin rash, and/or hives.
On Day 6, melphalan will be given over 30 minutes.
Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then once a week for a total of 4 doses.
On Day 7, after completion of chemotherapy, the blood or marrow stem cells that were collected earlier will be transplanted (given to your body) through the CVC over 30-45 minutes. This is the standard treatment.
On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to help decrease the risk of graft-versus-host disease.
G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a type of white blood cell) counts recover.
About 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
FOR PATIENTS RECEIVING FLUDARABINE, CYCLOPHOSPHAMIDE, CAMPATH-IH, RITUXIMAB,AND TBI:
TBI is designed to damage the DNA (the genetic material of cells) of cancer cells, which may kill the cancer cells.
Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain immune cells, which may cause the cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
On Days 1-3, alemtuzumab will be given over 30 minutes, fludarabine over 1 hour, and cyclophosphamide over 1 hour. Hydrocortisone and tacrolimus will be given by vein during this time to help prevent or ease side effects, such as chills, skin rash, and/or hives.
Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then once a week for a total of 4 doses.
On Day 5, after completion of chemotherapy, TBI will be given, and later on the same day, the blood stem cells that were collected earlier will be transplanted (given back to your body) through the CVC over 30-45 minutes. This is the standard treatment.
On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to help decrease the risk of graft-versus-host disease.
G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a type of white blood cell) counts recover.
About 80 patients will take part in this study. All will be enrolled at M. D. Anderson.
ALL PATIENTS:
Infusion of NK Cells and T-Cells:
A "boost" of NK cells or T-cells from a donor may be given after blood stem cell transplantation, depending on the disease status and the amount of donor cells in the blood.
If a complete remission (disappearance of cancer symptoms) is achieved at 3 months after transplantation with more than 80% donor T-cells, no additional T-cells will be given.
If donor T-cells are less than 80% in the blood, then a boost of NK cells or T-cells will be given. The type of cells given will depend on results of DNA testing that was done during the screening visit to check the presence of molecules that may be able to activate ("turn on") NK cells in a specific area of your DNA. The same type of cell infusion may be repeated 8 weeks later, if the percentage of donor T-cells does not reach 100% in the blood.
If active disease persists at 3 months after transplantation, 1 dose of rituximab will be given once a week, or NK cells or T-cells will be given between the second and third dose of rituximab. Infusion of NK cells or T-cells may be repeated every 6 weeks (up to 12 weeks), if the disease does not achieve complete remission with the first infusion of cells.
It will be required to stay in the hospital from about 2 weeks before the transplantation until about 2-3 weeks after the transplantation. The additional cells will be infused on an outpatient basis.
Epinephrine and antihistamines will be available at the bedside during the NK cell infusion to help treat any allergic reactions.
Study Visits:
It will be required to stay in the Houston area for about 100 days after the transplantation. During initial study visits, the following tests/procedures will be performed after the transplantation.
- Blood transfusions of blood and platelets as needed.
- Blood drawn (about 6 teaspoons) for routine tests.
- Blood drawn (about 6-10 tablespoons) to check the effects of the transplantation.
- Urine collected for routine tests.
- Imaging scans, such as the ones performed during the screening visit.
- Bone marrow biopsy performed, when it is necessary.
Between Days 25-35 after transplantation, and then at 3 months, CT scans, positron emission tomography (PET), routine blood draws (about 6 teaspoons), and a bone marrow biopsy/aspirate will be performed. These tests will be done to check the status of the disease.
Length of Study:
Length of time on this study up to about 3 years, unless the disease gets worse or any intolerable side effects are experienced.
Follow-up:
After Day 35, if the disease is in remission with 100% donor cells, an evaluation will be performed every 3 months during the first year and then every 6 months up to 3 years.
If the disease is not in remission by Days 90-100, CT scans, PET scans, routine blood tests (about 6 teaspoons), and a bone marrow biopsy/aspirate will be performed every 6-8 weeks (after each NK or T-cell infusion until remission is achieved ). Then, these tests will be repeated every 6 months.
This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. The use of NK cells is not FDA approved and commercially available. The use of the drugs and NK cells together in this study is investigational.
- Being tested
- ARA-C, BCNU, Campath-1H, Cyclophosphamide, Etoposide
- Keywords
- Lymphoma, Leukemia, B-Cell Lymphoid Malignancies, CLL, Cll/Small Lymphocytic Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma, Splenic Lymphoma, MALT, Lymphoplasmacytic Lymphoma, Burkitt's Lymphoma, ARA-C, BCNU, Campath-1H, Cytoxan, Etoposide, Fludarabine, Melphalan, Rituximab
- Medical subject headings
- Lymphoma, Leukemia, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARA-CDrug
Also called Cytarbine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
100 mg/m^2 IV Daily Over 1 Hour for 4 Days
BCNUDrug
Also called Carmustine, BiCNU
300 mg/m^2 IV Over 1 Hour for 1 Day
Campath-1HDrug
Also called Alemtuzumab, Campath
15 mg IV Daily Over 30 Minutes for 3 Days
CyclophosphamideDrug
Also called Cytoxan, Neosar
1000 mg/m^2 IV Daily Over 1 Hour for 3 Days
EtoposideDrug
Also called VePesid
100 mg/m^2 IV Daily Over 3 Hours for 4 Days
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
30 mg/m^2 IV Daily Over 1 Hour for 3 Days
MelphalanDrug
100 mg/m^2 IV Over 30 Minutes for 1 Day.
RituximabDrug
Also called Rituxan
375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks.
Allogeneic Stem Cell TransplantationOther
Stem Cell Infusion on Day 0.
Total body radiation (TBI)Radiation
TBI on Day 5 following chemotherapy, before stem cell infusion.
MethotrexateDrug
5 mg/m2 IV on Days +1, +3, and +6.
TacrolimusDrug
Also called Prograf
0.03 mg/kg/day IV starting on Day -2, to be given through day 60, tapered by 20% every week, then discontinue by day 90.
Adback NK or T CellProcedure or surgery
Adback natural killer (NK) cells or T cells after transplantation to enhance full engraftment of donor cells. Cell adback after transplantation applies only if there is no active GVHD, and no previous episode of grade II-IV GVHD.
| Study group | Role | What they receive |
|---|---|---|
| NK Cell/T-Cell Infusion | Experimental | Possible Cell Adback - infusion NK cells or T-cells from donor given after blood stem cell transplantation for either Reduced intensity chemotherapy of campath, modified BEAM regimen of Campath-IH 15 mg intravenous (IV) Daily for 3 Days + BEAM Daily for 4 days (BCNU 300 mg/m^2 IV, Etoposide 100 mg/m^2 IV, Ara-C 100 mg/m^2 IV Daily for 4 days and Melphalan 100 mg/m^2 IV Over 30 Minutes for 1 Day) + Rituximab 375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks]; or Non-myeloablative Preparative Regimen [Fludarabine 30 mg/m^2 IV Daily Over 1 Hour for 3 Days; Cyclophosphamide 1000 mg/m^2 IV Daily Over 1 Hour for 3 Days; Rituximab 375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks; Campath-IH 15 mg IV Daily Over 30 Minutes for 3 Days; plus Total Body radiation (TBI)]. Receives: Drug: ARA-C; Drug: BCNU; Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Fludarabine; Drug: Melphalan; Drug: Rituximab; Other: Allogeneic Stem Cell Transplantation; Radiation: Total body radiation (TBI); Drug: Methotrexate; Drug: Tacrolimus; Procedure: Adback NK or T Cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Treatment Related Mortality (TRM)
Number of participant deaths in 6 months of T- cell or Natural killer (NK) cell adback treatment.
Measured: 6 Months
Secondary outcomes (1)
One-year Disease-free Survival (DFS)
Efficacy (disease-free-survival) defined as number of participants still living, without disease progression following T- cell or Natural killer (NK) cell adback. One-year disease-free survival (DFS) time estimated using the Kaplan-Meier estimator. Patients who experience disease recurrence considered to be a treatment failure event.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Issa F. Khouri, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00536978
- Sponsor's protocol ID
- 2006-0230
- Status last verified
- Sep 2020
- First submitted
- 27 Sep 2007
- Last updated
- 24 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T-Cell or Natural Killer (NK) Cell Adback in Patients With Lymphoid Malignancies Receiving Allogeneic Stem Cell Transplantation With Campath-IH Containing Conditioning Regimens
- ClinicalTrials.gov ID
- NCT00536978
- Acronym / sponsor ID
- 2006-0230
- Keywords
- Lymphoma, Leukemia, B-Cell Lymphoid Malignancies, CLL, Cll/Small Lymphocytic Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 28 Sep 2007 (estimated)
- Results
- Posted 22 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective:
- To determine the safety of adback T- or Natural Killer (NK) cells in patients with lymphoid malignancies receiving allogeneic stem cell transplantation with Campath-IH containing conditioning regimen.
Secondary objective:
- To determine the efficacy (disease-free-survival) of this strategy.
Detailed description
NK Cells, T-Cells, and the Study Drugs:
NK and T-cells from a donor may decrease the risk of relapse (reappearance of disease) after stem cell transplantation. NK cells and T-cells are kinds of white blood cells. Both types of cells have the ability to fight infection and "kill" tumor cells in the body. NK cells are called "natural killers" because, unlike T-cells, NK cells do not need to be activated ("turned on") by an antigen (a foreign substance) in order to "attack" and "kill" tumor cells.
Screening Tests:
Before starting treatment on this study, "screening tests" will be performed to help the doctor determine eligibility to take part in this study.
- Physical exam.
- Blood drawn (about 6 1/2 to 8 tablespoons) for routine tests, to check the effects of the transplantation, and for a liver function test. This routine blood draw will also include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
- Urine collected for routine tests.
- Bone marrow biopsy performed to check the status of the disease. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
- Chest x-ray, computed tomography (CT) scans, and an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).
Study Treatment:
Treatment will begin within 30 days after the screening visit. All of the study drugs will be given through a central venous catheter (CVC) that will be left in place throughout treatment. 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 in more detail, and a signed separate consent form for this procedure is required
Before starting the chemotherapy in this study, 21 or more days must have elapsed since the last biological therapy, chemotherapy, radiotherapy, or other investigational therapy.
PATIENTS RECEIVING BEAM, CAMPATH-IH, AND RITUXIMAB AS CONDITIONING:
BEAM is designed to kill leukemia and lymphoma cells by inserting itself into the cell DNA (genetic material of cells).
Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain immune cells, which may cause the cells to die.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
On Day 1, BCNU will be given over 1 hour.
On Days 2-5, Ara-C will be given over 1 hour and etoposide over 3 hours. This will be repeated every 12 hours during these 4 days.
On Days 2-4, alemtuzumab will be given over 30 minutes. Hydrocortisone and tacrolimus will be given by vein during this time to help prevent or ease side effects, such as chills, skin rash, and/or hives.
On Day 6, melphalan will be given over 30 minutes.
Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then once a week for a total of 4 doses.
On Day 7, after completion of chemotherapy, the blood or marrow stem cells that were collected earlier will be transplanted (given to your body) through the CVC over 30-45 minutes. This is the standard treatment.
On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to help decrease the risk of graft-versus-host disease.
G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a type of white blood cell) counts recover.
About 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
FOR PATIENTS RECEIVING FLUDARABINE, CYCLOPHOSPHAMIDE, CAMPATH-IH, RITUXIMAB,AND TBI:
TBI is designed to damage the DNA (the genetic material of cells) of cancer cells, which may kill the cancer cells.
Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain immune cells, which may cause the cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
On Days 1-3, alemtuzumab will be given over 30 minutes, fludarabine over 1 hour, and cyclophosphamide over 1 hour. Hydrocortisone and tacrolimus will be given by vein during this time to help prevent or ease side effects, such as chills, skin rash, and/or hives.
Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then once a week for a total of 4 doses.
On Day 5, after completion of chemotherapy, TBI will be given, and later on the same day, the blood stem cells that were collected earlier will be transplanted (given back to your body) through the CVC over 30-45 minutes. This is the standard treatment.
On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to help decrease the risk of graft-versus-host disease.
G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a type of white blood cell) counts recover.
About 80 patients will take part in this study. All will be enrolled at M. D. Anderson.
ALL PATIENTS:
Infusion of NK Cells and T-Cells:
A "boost" of NK cells or T-cells from a donor may be given after blood stem cell transplantation, depending on the disease status and the amount of donor cells in the blood.
If a complete remission (disappearance of cancer symptoms) is achieved at 3 months after transplantation with more than 80% donor T-cells, no additional T-cells will be given.
If donor T-cells are less than 80% in the blood, then a boost of NK cells or T-cells will be given. The type of cells given will depend on results of DNA testing that was done during the screening visit to check the presence of molecules that may be able to activate ("turn on") NK cells in a specific area of your DNA. The same type of cell infusion may be repeated 8 weeks later, if the percentage of donor T-cells does not reach 100% in the blood.
If active disease persists at 3 months after transplantation, 1 dose of rituximab will be given once a week, or NK cells or T-cells will be given between the second and third dose of rituximab. Infusion of NK cells or T-cells may be repeated every 6 weeks (up to 12 weeks), if the disease does not achieve complete remission with the first infusion of cells.
It will be required to stay in the hospital from about 2 weeks before the transplantation until about 2-3 weeks after the transplantation. The additional cells will be infused on an outpatient basis.
Epinephrine and antihistamines will be available at the bedside during the NK cell infusion to help treat any allergic reactions.
Study Visits:
It will be required to stay in the Houston area for about 100 days after the transplantation. During initial study visits, the following tests/procedures will be performed after the transplantation.
- Blood transfusions of blood and platelets as needed.
- Blood drawn (about 6 teaspoons) for routine tests.
- Blood drawn (about 6-10 tablespoons) to check the effects of the transplantation.
- Urine collected for routine tests.
- Imaging scans, such as the ones performed during the screening visit.
- Bone marrow biopsy performed, when it is necessary.
Between Days 25-35 after transplantation, and then at 3 months, CT scans, positron emission tomography (PET), routine blood draws (about 6 teaspoons), and a bone marrow biopsy/aspirate will be performed. These tests will be done to check the status of the disease.
Length of Study:
Length of time on this study up to about 3 years, unless the disease gets worse or any intolerable side effects are experienced.
Follow-up:
After Day 35, if the disease is in remission with 100% donor cells, an evaluation will be performed every 3 months during the first year and then every 6 months up to 3 years.
If the disease is not in remission by Days 90-100, CT scans, PET scans, routine blood tests (about 6 teaspoons), and a bone marrow biopsy/aspirate will be performed every 6-8 weeks (after each NK or T-cell infusion until remission is achieved ). Then, these tests will be repeated every 6 months.
This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. The use of NK cells is not FDA approved and commercially available. The use of the drugs and NK cells together in this study is investigational.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK Cell/T-Cell Infusion | Experimental | Drug: ARA-C, Drug: BCNU, Drug: Campath-1H, Drug: Cyclophosphamide, Drug: Etoposide, Drug: Fludarabine, Drug: Melphalan, Drug: Rituximab, Other: Allogeneic Stem Cell Transplantation, Radiation: Total body radiation (TBI), Drug: Methotrexate, Drug: Tacrolimus, Procedure: Adback NK or T CellPossible Cell Adback - infusion NK cells or T-cells from donor given after blood stem cell transplantation for either Reduced intensity chemotherapy of campath, modified BEAM regimen of Campath-IH 15 mg intravenous (IV) Daily for 3 Days + BEAM Daily for 4 days (BCNU 300 mg/m^2 IV, Etoposide 100 mg/m^2 IV, Ara-C 100 mg/m^2 IV Daily for 4 days and Melphalan 100 mg/m^2 IV Over 30 Minutes for 1 Day) + Rituximab 375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks]; or Non-myeloablative Preparative Regimen [Fludarabine 30 mg/m^2 IV Daily Over 1 Hour for 3 Days; Cyclophosphamide 1000 mg/m^2 IV Daily Over 1 Hour for 3 Days; Rituximab 375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks; Campath-IH 15 mg IV Daily Over 30 Minutes for 3 Days; plus Total Body radiation (TBI)]. |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Up to 70 years of age.
- B-cell lymphoid malignancies (those with CD20 negative disease at their diagnosis will not receive rituximab): This includes CLL/small lymphocytic lymphoma, follicular lymphoma, mantle cell, diffuse large cell, Splenic lymphoma, Mucosa-Associated Lymphoid Tissue (MALT), lymphoplasmacytic lymphoma and Burkitt's lymphoma.
- Patients in relapse or considered at high risk for relapse.
- In order to increase the chance of KIR-mismatching between recipient and donor, a 9/10 matched (mismatched locus C ) unrelated donor would be preferable. If a mismatched donor is not available, then a fully-matched unrelated donor or other 9/10 matched unrelated donor will be considered.
- A sibling donor who is 9/10 matched may also be allowed.
Key exclusion criteria (13 listed)
- Past history of anaphylaxis following exposure to CAMPATH-IH or Rituximab
- Patient with active Central Nervous System (CNS) disease.
- Positive Beta human chorionic gonadotrophin (hCG) text in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization, or currently breast-feeding.
- Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
- Patients with other malignancies diagnosed within 2 years prior to Study registration (except skin squamous cell carcinoma).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARA-CAlso: Cytarbine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride100 mg/m^2 IV Daily Over 1 Hour for 4 Days | Drug | NK Cell/T-Cell Infusion |
| BCNUAlso: Carmustine, BiCNU300 mg/m^2 IV Over 1 Hour for 1 Day | Drug | NK Cell/T-Cell Infusion |
| Campath-1HAlso: Alemtuzumab, Campath15 mg IV Daily Over 30 Minutes for 3 Days | Drug | NK Cell/T-Cell Infusion |
| CyclophosphamideAlso: Cytoxan, Neosar1000 mg/m^2 IV Daily Over 1 Hour for 3 Days | Drug | NK Cell/T-Cell Infusion |
| EtoposideAlso: VePesid100 mg/m^2 IV Daily Over 3 Hours for 4 Days | Drug | NK Cell/T-Cell Infusion |
| FludarabineAlso: Fludarabine Phosphate, Fludara30 mg/m^2 IV Daily Over 1 Hour for 3 Days | Drug | NK Cell/T-Cell Infusion |
| Melphalan100 mg/m^2 IV Over 30 Minutes for 1 Day. | Drug | NK Cell/T-Cell Infusion |
| RituximabAlso: Rituxan375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks. | Drug | NK Cell/T-Cell Infusion |
| Allogeneic Stem Cell TransplantationStem Cell Infusion on Day 0. | Other | NK Cell/T-Cell Infusion |
| Total body radiation (TBI)TBI on Day 5 following chemotherapy, before stem cell infusion. | Radiation | NK Cell/T-Cell Infusion |
| Methotrexate5 mg/m2 IV on Days +1, +3, and +6. | Drug | NK Cell/T-Cell Infusion |
| TacrolimusAlso: Prograf0.03 mg/kg/day IV starting on Day -2, to be given through day 60, tapered by 20% every week, then discontinue by day 90. | Drug | NK Cell/T-Cell Infusion |
| Adback NK or T CellAdback natural killer (NK) cells or T cells after transplantation to enhance full engraftment of donor cells. Cell adback after transplantation applies only if there is no active GVHD, and no previous episode of grade II-IV GVHD. | Procedure or surgery | NK Cell/T-Cell Infusion |
Primary outcome
6-month Treatment Related Mortality (TRM)
Time frame: 6 Months
Number of participant deaths in 6 months of T- cell or Natural killer (NK) cell adback treatment.
1 secondary outcome
One-year Disease-free Survival (DFS)
Time frame: 1 Year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Issa F. Khouri, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ARA-C, BCNU and Campath-1H in people with Lymphoma and Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month Treatment Related Mortality (TRM) (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2020; AzTrials last refreshed its copy on 6 Nov 2026.