Hematologic NeoplasmPhase 1NCT00005785
Stem Cell (Modified Bone Marrow) Transplantation in HIV-Infected Patients With Blood Cancer
A Phase 1 study testing GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV in people with Hematologic Neoplasm and HIV Infection, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hematologic Neoplasm, HIV Infection
- What is being tested?
- GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1999to Nov 2001
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
PATIENTS:
Patients with hematologic malignancies curable by allogeneic BMT not currently considered for transplant because of HIV positivity.
Chronic myelogenous leukemia (CML): chronic phase.
Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.
Acute myelogenous leukemia (AML): AML in first complete or partial remission. (Exceptions: AML with good risk karyotypes: AML M3t, AML M4Eo, AML t. All AML in second or subsequent complete remission.)
Myelodysplastic syndromes: refractory anemia (failing ATG and/or CSA) to early transformation to acute leukemia. Chronic myelomonocytic leukemia and myeloproliferative disease.
Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, in complete or partial remission, Mantle cell lymphoma, relapsed Hodgkin's and non-Hodgkin's lymphoma.
Multiple myeloma in remission following chemotherapy.
No major organ dysfunction precluding transplantation.
DLCO greater than 40 percent predicted.
Left ventricular ejection fraction greater than 30 percent.
ECOG performance status of 0 to 2.
DONOR:
HLA identical sibling donor.
Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease).
Informed consent given.
DONOR AND PATIENT:
Must not be pregnant or lactating.
Must be between 18 and 80 years of age.
Must not have ECOG performance status of 3 or more. Must not have psychiatric disorder or mental deficiency of the patient or the donor sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
Must not have a major anticipated illness or organ failure incompatible with survival from BMT as determined by your NIH physician (including encephalopathy, cardiomyopathy, and hepatitis.)
Must not have DLCO less than 40 percent predicted.
Must not have glomerular filtration rate less than 40.
Must not have serum bilirubin greater than 4 mg/dl, transaminases greater than 4x upper limit of normal.
Donor must be HIV negative. Donors who are positive for HBV, HCV or HTLV will be used at the discretion of the investigator.
Must not have other malignant diseases liable to relapse or progress within 5 years.
Donor must be fit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, Maryland, 20892
About this study
Official title: Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells (PBPC) for Hematologic Malignancies in HIV Positive Adults
This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients.
HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure. This study uses a modified procedure, transplanting stem cells instead of bone marrow, designed to be less dangerous for such patients. Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection. The procedure in this study differs from standard bone marrow transplantation in three ways:
Read more
Stem cells will be transplanted instead of bone marrow. (Stem cells, which are produced by the bone marrow, mature into the different blood components-white and red cells and platelets.) The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream. The cells will then be collected from the donor by apheresis, a procedure in which whole blood is drawn, the stem cells separated and removed, and the rest of the blood returned to the donor.);
The procedure will use lower doses of chemotherapy than the conventional method, and will not use radiation therapy; or
A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells, rendering future cells that develop from resistance to the virus.
Prospective patients will be tested for matching with an HIV-negative donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, etc.) to determine eligibility for the study. Study participants will then undergo apheresis to collect white blood cells called lymphocytes. Stem cells will be collected from the donor. Half the donated cells will have the HIV-resistant gene inserted; the other half will have a "control" gene inserted. Additional stem cells collected a second day will not be manipulated. All the donor cells will be frozen until transplantation.
Patients will be given drugs (cyclophosphamide, fludarabine and cyclosporin) to prevent the donated cells from being rejected and to prevent them from damaging the patient's organs. The thawed stem cells will then be infused through a vein. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years.
Read the detailed description
Adult patients with myelodysplasia, leukemia, and non-Hodgkin's lymphoma can be cured by allogeneic bone marrow transplantation (BMT). This curative effect has until now been ascribed to the intense chemoradiotherapy used to condition the recipient for transplantation. The assumption that the curative effect of allogeneic transplantation rests in the ability to deliver very high doses of chemoradiotherapy has led to the restriction of allogeneic transplantation to those recipient patients whose overall status would permit the use of such intense conditioning. As a result, HIV positivity has generally appeared as an exclusion criteria to allogeneic transplantation for hematologic malignancies. Additionally, early studies of allogeneic BMT in HIV patients suggested no benefit in controlling the progression to AIDS.
Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8 positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft versus leukemia (GVL) effect, and this GVL effect is area of intense interest both at the NIH and elsewhere. In fact, early attempts to decrease treatment related mortality in chronic myelogenous leukemia (CML) patients undergoing allogeneic BMT by T-cell depletion of the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in the donor graft accounted for a significant portion of the cure rate in this disease. This GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes can induce a complete and durable remission.
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated for engraftment efficacy and toxicity in a number of transplant centers. Preliminary data including our own experience with 13 patients undergoing this type of procedure have shown a high rate of complete donor engraftment, low toxicity, and preservation of the GVL effect. Two recent published studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant related complications and mortality.
The decreased risk of transplant related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates and may allow successful application in patients infected with HIV. In this study, we will assess the safety and efficacy of nonmyeloablative transplantation in patients with HIV infection. Moreover, the introduction of an HIV resistance vector into a portion of the allogeneic graft provides a unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the self renewing stem cell.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality, disease free survival, as well as overall survival, and overall level and persistence of progeny of gene modified cells.
- Conditions
- Hematologic Neoplasm, HIV Infection
- Being tested
- GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV
- Keywords
- Peripheral Blood Stem Cells, Engraftment, Graft vs. Host Disease, Graft-Versus-Leukemia, Donor Apheresis, Cyclophosphamide, Fludarabine, HIV, AIDS, Gene Therapy, Chronic Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Chronic Lymphocytic Leukemia
- Medical subject headings
- Hematologic Neoplasms, HIV Infections, Graft vs Host Disease, Acquired Immunodeficiency Syndrome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RVDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2000 (estimated)
- Study startSep 1999
- Study completionNov 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic NeoplasmStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 1
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005785
- Sponsor's protocol ID
- 990167
- Other IDs
- 99-DK-0167
- Status last verified
- Nov 2001
- First submitted
- 3 Jun 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells (PBPC) for Hematologic Malignancies in HIV Positive Adults
- ClinicalTrials.gov ID
- NCT00005785
- Acronym / sponsor ID
- 990167
- Conditions
- Hematologic Neoplasm, HIV Infection
- Keywords
- Peripheral Blood Stem Cells, Engraftment, Graft vs. Host Disease, Graft-Versus-Leukemia, Donor Apheresis, Cyclophosphamide, Fludarabine, HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Sep 1999
- Study completion
- Nov 2001
- First posted
- 5 Jun 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients.
HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure. This study uses a modified procedure, transplanting stem cells instead of bone marrow, designed to be less dangerous for such patients. Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection. The procedure in this study differs from standard bone marrow transplantation in three ways:
Stem cells will be transplanted instead of bone marrow. (Stem cells, which are produced by the bone marrow, mature into the different blood components-white and red cells and platelets.) The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream. The cells will then be collected from the donor by apheresis, a procedure in which whole blood is drawn, the stem cells separated and removed, and the rest of the blood returned to the donor.);
The procedure will use lower doses of chemotherapy than the conventional method, and will not use radiation therapy; or
A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells, rendering future cells that develop from resistance to the virus.
Prospective patients will be tested for matching with an HIV-negative donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, etc.) to determine eligibility for the study. Study participants will then undergo apheresis to collect white blood cells called lymphocytes. Stem cells will be collected from the donor. Half the donated cells will have the HIV-resistant gene inserted; the other half will have a "control" gene inserted. Additional stem cells collected a second day will not be manipulated. All the donor cells will be frozen until transplantation.
Patients will be given drugs (cyclophosphamide, fludarabine and cyclosporin) to prevent the donated cells from being rejected and to prevent them from damaging the patient's organs. The thawed stem cells will then be infused through a vein. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years.
Detailed description
Adult patients with myelodysplasia, leukemia, and non-Hodgkin's lymphoma can be cured by allogeneic bone marrow transplantation (BMT). This curative effect has until now been ascribed to the intense chemoradiotherapy used to condition the recipient for transplantation. The assumption that the curative effect of allogeneic transplantation rests in the ability to deliver very high doses of chemoradiotherapy has led to the restriction of allogeneic transplantation to those recipient patients whose overall status would permit the use of such intense conditioning. As a result, HIV positivity has generally appeared as an exclusion criteria to allogeneic transplantation for hematologic malignancies. Additionally, early studies of allogeneic BMT in HIV patients suggested no benefit in controlling the progression to AIDS.
Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8 positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft versus leukemia (GVL) effect, and this GVL effect is area of intense interest both at the NIH and elsewhere. In fact, early attempts to decrease treatment related mortality in chronic myelogenous leukemia (CML) patients undergoing allogeneic BMT by T-cell depletion of the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in the donor graft accounted for a significant portion of the cure rate in this disease. This GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes can induce a complete and durable remission.
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated for engraftment efficacy and toxicity in a number of transplant centers. Preliminary data including our own experience with 13 patients undergoing this type of procedure have shown a high rate of complete donor engraftment, low toxicity, and preservation of the GVL effect. Two recent published studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant related complications and mortality.
The decreased risk of transplant related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates and may allow successful application in patients infected with HIV. In this study, we will assess the safety and efficacy of nonmyeloablative transplantation in patients with HIV infection. Moreover, the introduction of an HIV resistance vector into a portion of the allogeneic graft provides a unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the self renewing stem cell.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality, disease free survival, as well as overall survival, and overall level and persistence of progeny of gene modified cells.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV in people with Hematologic Neoplasm and HIV Infection, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
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 4 Mar 2008; AzTrials last refreshed its copy on 26 Oct 2026.