Acute Lymphoblastic LeukemiaNCT01200017
Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant
A study testing CD34+ enriched, T Cell Depleted donor stem cell product in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Christopher Dvorak at 1 site in United States.
Trial summary
This protocol provides expanded access to bone marrow transplants for children who lack a histocompatible (tissue matched) stem cell or bone marrow donor when an alternative donor (unrelated donor or half-matched related donor) is available to donate. Read more about this study
- Who is it for?
- Ages 2 months to 30 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia
- What is being tested?
- CD34+ enriched, T Cell Depleted donor stem cell product
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- 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 2 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- >2 months - 30 years
- Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation according to standard practice guidelines for including patients for transplant as outlined in UCSF Pediatric Bone Marrow Transplant (BMT) Standard Operating Procedure (SOP) #206.04. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, inborn errors of metabolism and immunodeficiencies. Patient with Fanconi's Anemia will be eligible regardless of match with donor.
- Patients with acute leukemia (AML excepted) or lymphoma must be in remission at the time of transplant.
- Patients must lack a healthy human leukocyte antigen (HLA)-identical related donor.
- Recipient or authorized guardian must sign informed consent for this study.
- If recipient is female and of child-bearing age, negative pregnancy test.
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- Patient must have a healthy, willing mismatched related or an unrelated donor who is:
- Able to receive Granulocyte colony-stimulating factor (G-CSF) +/- Plerixafor and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
- For Related donor: sibling, half-sibling, parent, cousin, aunt, uncle or grandparent will all be considered eligible.
- For Related donor: HLA antigen genotypic match ≥ 4/8 and ≤ 7/8 (haplocompatible).
- For unrelated donor: 6/8 or 7/8 HLA antigen match (if two mismatches, they must be at different loci).
- Complete medical history, physical and screening for infectious diseases that are acceptable for donation.
- If donor is female and of child-bearing age, negative pregnancy test.
- Absence of anti-HLA antibodies in recipient directed against donor antigens.
- Donor must be willing to sign informed consent for this study. If donor is < 18 years of age, donor must be willing to give assent and parents willing to sign informed consent.
- Be suitable for an autologous gene-modified transplant:
- Using either bone marrow or cytokine-mobilized peripheral blood stem cells (PBSC).
- Patient or authorized guardian must sign informed consent for this study.
- For unrelated donors: Per New Algorithm, Jan. 14, 2016, effective immediately, National Marrow Donor Program (NMDP) "Be The Match" is adopting a revised algorithm for determining if a donor is a research subject on their recipient's research protocol: The NMDP will inform the donor of the activities and the use of donor's apheresis product to be used in this study and obtain written consent from the donor. Transplant centers are sent documentation of the donor consent to participate in the research support activities. (The revised algorithm can be found on the "Be the Match Clinical Network")
- Criteria to consider when choosing among related haplo donors:
- CMV positive donor is preferred over other factors. CMV negative donor can be used only if recipient is CMV negative.
- HLA disparity i.e. 2 Ag mismatch preferred over 3 Ag mismatch; Drβ1 match preferred over class I match; HLA-C matched preferred over A and B match.
- killer immunoglobulin-like receptor (KIR) mismatch in GVH direction is preferred for patients with malignant disorders
- ABO compatibility
- Age ≥ 2 months
Who cannot join
- Patient with an anticipated life expectancy of < 1 month
- Active infectious hepatitis or cytomegalovirus (CMV) disease (organ involvement)
- Human immunodeficiency virus (HIV) or Human T-lymphotropic virus (HTLV-I/II) infection
- Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used.
- Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used.
- Pulmonary diffusion capacity (corrected for hemoglobin), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) <60% of predicted or oxygen saturation (O2 sat) > 94% on room air if unable to perform pulmonary function tests (PFTs); can be lower if a reduced intensity conditioning regimen is used.
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- Serum alanine aminotransferase (ALT) > 5 x upper limit of normal (can be up to 10x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2.
- Performance score (Lansky/Karnofsky) < 50
- Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: An Expanded Access Study of the Feasibility of Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients
This protocol provides expanded access to bone marrow transplants for children who lack a histocompatible (tissue matched) stem cell or bone marrow donor when an alternative donor (unrelated donor or half-matched related donor) is available to donate. In this procedure, some of the blood forming cells (the stem cells) are collected from the blood of a partially human leukocyte antigen (HLA) matched (haploidentical) donor and are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow). A major problem after a transplant from an alternative donor is increased risk of Graft-versus-Host Disease (GVHD), which occurs when donor T cells (white blood cells that are involved with the body's immune response) attack other tissues or organs like the skin, liver and intestines of the transplant recipient. In this study, stem cells that are obtained from a partially-matched donor will be highly purified using the investigational CliniMACS® stem cell selection device in an effort to achieve specific T cell target values. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in a high risk patient population by limiting the complication of GVHD.
Read the detailed description
Patients will be enrolled with alternative (mismatched/haplocompatible) related donors or unrelated donors either for an initial transplant or as a rescue following rejection of a previous graft or relapse following a previous transplant. For patients with mismatched related donors, the majority of clinical experience has been with a T cell-depleted PBSC product. Currently, no FDA-approved method for T cell depletion exists. Recent experience with the CliniMACS® device has produced excellent results with a 70-75% survival in children, many of whom were high risk patients.
Patients that receive transplants from unrelated donors usually receive stem cells that are not T cell-depleted. However, this is associated with a high risk of GVHD. The excellent results with mismatched related donor transplants justify expanding this approach to unrelated donor transplant recipients if the HLA mismatch is sufficiently great. It is anticipated that the use of the CliniMACS® device will result in a very low risk of GVHD without the need for post-transplant immunosuppression. The outcomes in relatively small studies for children receiving unrelated donor transplants using the CliniMACS® have been comparable to or better than those receiving T replete transplants with post-transplant immunosuppression.
This protocol will allow the use of patient-specific conditioning regimens. Some patients have contraindications to certain components of the conditioning regimen used for our ongoing study under BB-IND 8817 (CC# 01151). An example is a patient with pre-existing organ dysfunction that would be better served by the use of a reduced intensity conditioning regimen. Another example is a patient for whom total body irradiation is contraindicated due to very young age or prior radiation therapy. Finally, patients who would be otherwise eligible for the predecessor study but who do not have an eligible related donor or a closely matched unrelated donor would be eligible for this study. The target CD3+ T cell dose that will be given will be 3 x 10^4/kg. The University of California, San Francisco Protocol CC#01151 uses a dose of 3 x 10^4/kg. The T cell dose in the graft is usually < 1 x 10^4/kg after processing and T cells are added to the product.
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndrome, Lymphomas, Bone Marrow Failure
- Being tested
- CD34+ enriched, T Cell Depleted donor stem cell product
- Keywords
- T cell depleted, Matched unrelated donors, Haplocompatible donors, Graft vs Host Disease, Hemoglobinopathies, Leukemia, Leukemia, Lymphoid, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Myelodysplastic Syndromes, Preleukemia, Osteopetrosis, Pancytopenia, Immune System Diseases, Hematologic Diseases, Genetic Diseases, Inborn, Neoplasms by Histologic Type
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Lymphoma, Bone Marrow Failure Disorders, Hemoglobinopathies, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34+ enriched, T Cell Depleted donor stem cell productBiological
Also called bone marrow transplant
stem cell transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- 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
- Expanded access
Sponsor and investigators
- Lead sponsor
- Christopher Dvorak
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christopher Dvorak, University of California, San Francisco
- Investigators
- Christopher Dvorak, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01200017
- Sponsor's protocol ID
- 10082
- Other IDs
- NCI-2020-02478
- Status last verified
- May 2021
- First submitted
- 9 Sep 2010
- Last updated
- 27 May 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Expanded Access Study of the Feasibility of Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT01200017
- Acronym / sponsor ID
- 10082
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndrome, Lymphomas, Bone Marrow Failure
- Keywords
- T cell depleted, Matched unrelated donors, Haplocompatible donors, Graft vs Host Disease, Hemoglobinopathies, Leukemia, Leukemia, Lymphoid, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- Christopher DvorakUniversity, hospital or other
- First posted
- 13 Sep 2010 (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 protocol provides expanded access to bone marrow transplants for children who lack a histocompatible (tissue matched) stem cell or bone marrow donor when an alternative donor (unrelated donor or half-matched related donor) is available to donate. In this procedure, some of the blood forming cells (the stem cells) are collected from the blood of a partially human leukocyte antigen (HLA) matched (haploidentical) donor and are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow). A major problem after a transplant from an alternative donor is increased risk of Graft-versus-Host Disease (GVHD), which occurs when donor T cells (white blood cells that are involved with the body's immune response) attack other tissues or organs like the skin, liver and intestines of the transplant recipient. In this study, stem cells that are obtained from a partially-matched donor will be highly purified using the investigational CliniMACS® stem cell selection device in an effort to achieve specific T cell target values. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in a high risk patient population by limiting the complication of GVHD.
Detailed description
Patients will be enrolled with alternative (mismatched/haplocompatible) related donors or unrelated donors either for an initial transplant or as a rescue following rejection of a previous graft or relapse following a previous transplant. For patients with mismatched related donors, the majority of clinical experience has been with a T cell-depleted PBSC product. Currently, no FDA-approved method for T cell depletion exists. Recent experience with the CliniMACS® device has produced excellent results with a 70-75% survival in children, many of whom were high risk patients.
Patients that receive transplants from unrelated donors usually receive stem cells that are not T cell-depleted. However, this is associated with a high risk of GVHD. The excellent results with mismatched related donor transplants justify expanding this approach to unrelated donor transplant recipients if the HLA mismatch is sufficiently great. It is anticipated that the use of the CliniMACS® device will result in a very low risk of GVHD without the need for post-transplant immunosuppression. The outcomes in relatively small studies for children receiving unrelated donor transplants using the CliniMACS® have been comparable to or better than those receiving T replete transplants with post-transplant immunosuppression.
This protocol will allow the use of patient-specific conditioning regimens. Some patients have contraindications to certain components of the conditioning regimen used for our ongoing study under BB-IND 8817 (CC# 01151). An example is a patient with pre-existing organ dysfunction that would be better served by the use of a reduced intensity conditioning regimen. Another example is a patient for whom total body irradiation is contraindicated due to very young age or prior radiation therapy. Finally, patients who would be otherwise eligible for the predecessor study but who do not have an eligible related donor or a closely matched unrelated donor would be eligible for this study. The target CD3+ T cell dose that will be given will be 3 x 10^4/kg. The University of California, San Francisco Protocol CC#01151 uses a dose of 3 x 10^4/kg. The T cell dose in the graft is usually < 1 x 10^4/kg after processing and T cells are added to the product.
Study design
Who may qualify
- Ages
- 2 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- >2 months - 30 years
- Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation according to standard practice guidelines for including patients for transplant as outlined in UCSF Pediatric Bone Marrow Transplant (BMT) Standard Operating Procedure (SOP) #206.04. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, inborn errors of metabolism and immunodeficiencies. Patient with Fanconi's Anemia will be eligible regardless of match with donor.
- Patients with acute leukemia (AML excepted) or lymphoma must be in remission at the time of transplant.
- Patients must lack a healthy human leukocyte antigen (HLA)-identical related donor.
- Recipient or authorized guardian must sign informed consent for this study.
Key exclusion criteria (9 listed)
- Patient with an anticipated life expectancy of < 1 month
- Active infectious hepatitis or cytomegalovirus (CMV) disease (organ involvement)
- Human immunodeficiency virus (HIV) or Human T-lymphotropic virus (HTLV-I/II) infection
- Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used.
- Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used.
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 |
|---|---|---|
| CD34+ enriched, T Cell Depleted donor stem cell productAlso: bone marrow transplantstem cell transplant | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2021.
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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.
Christopher Dvorak, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CD34+ enriched, T Cell Depleted donor stem cell product in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Christopher Dvorak 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 25 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 27 May 2021. 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.
Are results available for this study?
Results are not available in the source record.
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 27 May 2021; AzTrials last refreshed its copy on 26 Oct 2026.