Congenital Amegakaryocytic ThrombocytopeniaPhase 1NCT00295971
Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
A Phase 1 study testing anti-thymocyte globulin, therapeutic allogeneic lymphocytes and fludarabine phosphate in people with Congenital Amegakaryocytic Thrombocytopenia and Leukemia, run by University of California, San Francisco at 2 sites in United States.
Trial summary
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Congenital Amegakaryocytic Thrombocytopenia, Leukemia, Myelodysplastic Syndromes
- What is being tested?
- anti-thymocyte globulin, therapeutic allogeneic lymphocytes and fludarabine phosphate
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2005to Dec 2011
- 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 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
DISEASE CHARACTERISTICS:
- Diagnosis of one of the following:
- Acute lymphoblastic leukemia in ≥ 2nd remission or delayed remission induction
- High-risk myelodysplastic syndromes
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelogenous leukemia in second chronic phase
- No accelerated phase (> 5% blasts in marrow)
- Juvenile myelomonocytic leukemia
- Acute nonlymphoblastic leukemia in > 1st remission or induction failure and < 30% blasts in marrow
- Severe aplastic anemia, defined as absolute neutrophil count < 500/mm^3 and platelet and/or red blood cell transfusion dependent
- Unresponsive to immunosuppressive therapy
- No Fanconi's anemia
- Congenital marrow aplasias unresponsive to cytokines and transfusion dependent
- Inherited immunodeficiency disease involving neutrophils or lymphocytes, including any of the following:
- Chediak-Higashi disease
- Wiskott-Aldrich syndrome
- Combined immunodeficiency disease (Nezelof's)
- Hyper IgM syndrome
- No relapsed disease
- Haplocompatible related donor, including parent, cousin, aunt, uncle, grandparent, half-sibling, or sibling (≥ 12 years of age), available
- 2 or 3 HLA antigen mismatch
- At least a 3 HLA antigen genotypic match
- No closely matched related or unrelated donor available in sufficient time to do the transplant
PATIENT CHARACTERISTICS:
- No active hepatitis or cytomegalovirus infection
- Cardiac ejection fraction ≥ 30%
- Creatinine clearance ≥ 70 mL/min
- DLCO ≥ 70% of predicted
- No active infection
- No HIV positivity
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
Read the detailed description
OBJECTIVES:
- Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted, haplocompatible allogeneic hematopoietic stem cell transplantation in children with high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital cytopenias, or primary immunodeficiency diseases.
- Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination with lower doses of antithymocyte globulin in these patients.
- Determine the engraftment rate in patients treated with this regimen.
- Define T-cell reconstitution in these patients.
- Determine the toxicity and effects of administering stem cell and T-cell boosts after transplantation on hematopoiesis and immune reconstitution in these patients.
OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).
- Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9 to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12 hours on day -6, and ATG IV on days -5 to -2.
- Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
- Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may receive donor CD3+ cells at 4-week intervals.
- Donor stem cell boost: Patients with engraftment but either cytokine or transfusion dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.
Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.
After the completion of study treatment, patients are followed periodically for 5 years and then every 5 years thereafter.
PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.
- Conditions
- Congenital Amegakaryocytic Thrombocytopenia, Leukemia, Myelodysplastic Syndromes, Severe Congenital Neutropenia
- Being tested
- anti-thymocyte globulin, therapeutic allogeneic lymphocytes, fludarabine phosphate, thiotepa, allogeneic bone marrow transplantation
- Keywords
- childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, secondary acute myeloid leukemia, juvenile myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, severe congenital neutropenia, congenital amegakaryocytic thrombocytopenia, childhood chronic myelogenous leukemia, childhood myelodysplastic syndromes
- Medical subject headings
- Congenital amegakaryocytic thrombocytopenia, Leukemia, Myelodysplastic Syndromes, Neutropenia, Severe Congenital, Autosomal Recessive 3, Leukemia, Myelomonocytic, Juvenile, Leukemia, Myeloid, Chronic-Phase, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
therapeutic allogeneic lymphocytesBiological
thiotepaDrug
allogeneic bone marrow transplantationProcedure or surgery
allogeneic hematopoietic stem cell transplantationProcedure or surgery
in vitro-treated peripheral blood stem cell transplantationProcedure or surgery
total-body irradiationRadiation
| Study group | Role | What they receive |
|---|---|---|
| Single arm of transplant | Experimental | Receiving haplocompatible T cell depleted peripheral blood stem cell transplant Receives: Biological: anti-thymocyte globulin; Biological: therapeutic allogeneic lymphocytes; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: total-body irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment at 4 weeks post bone marrow transplantation through 100 days
Measured: 100 days
Secondary outcomes (4)
Survival assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Measured: 1 year
Disease-free survival and infection assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Measured: 1 year
Graft-versus-host disease assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Measured: 2 years
CD4 count in blood < 100/mm³ at 12 weeks
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2006 (estimated)
- Study startApr 2005
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Amegakaryocytic ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Morton Cowan, University of California, San Francisco
- Investigators
- Morton J. Cowan, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00295971
- Sponsor's protocol ID
- CDR0000462168
- Other IDs
- UCSF-01151, UCSF-H411-17122-07
- Status last verified
- Nov 2012
- First submitted
- 23 Feb 2006
- Last updated
- 12 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT00295971
- Acronym / sponsor ID
- CDR0000462168
- Conditions
- Congenital Amegakaryocytic Thrombocytopenia, Leukemia, Myelodysplastic Syndromes, Severe Congenital Neutropenia
- Keywords
- childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, secondary acute myeloid leukemia, juvenile myelomonocytic leukemia, chronic phase chronic myelogenous leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2005
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 24 Feb 2006 (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.
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
Detailed description
OBJECTIVES:
- Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted, haplocompatible allogeneic hematopoietic stem cell transplantation in children with high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital cytopenias, or primary immunodeficiency diseases.
- Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination with lower doses of antithymocyte globulin in these patients.
- Determine the engraftment rate in patients treated with this regimen.
- Define T-cell reconstitution in these patients.
- Determine the toxicity and effects of administering stem cell and T-cell boosts after transplantation on hematopoiesis and immune reconstitution in these patients.
OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).
- Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9 to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12 hours on day -6, and ATG IV on days -5 to -2.
- Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
- Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may receive donor CD3+ cells at 4-week intervals.
- Donor stem cell boost: Patients with engraftment but either cytokine or transfusion dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.
Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.
After the completion of study treatment, patients are followed periodically for 5 years and then every 5 years thereafter.
PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm of transplant | Experimental | Biological: anti-thymocyte globulin, Biological: therapeutic allogeneic lymphocytes, Drug: fludarabine phosphate, Drug: thiotepa, Procedure: allogeneic bone marrow transplantation, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: in vitro-treated peripheral blood stem cell transplantation, Radiation: total-body irradiationReceiving haplocompatible T cell depleted peripheral blood stem cell transplant |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 |
|---|---|---|
| anti-thymocyte globulin | Biological | Single arm of transplant |
| therapeutic allogeneic lymphocytes | Biological | Single arm of transplant |
| fludarabine phosphate | Drug | Single arm of transplant |
| thiotepa | Drug | Single arm of transplant |
| allogeneic bone marrow transplantation | Procedure or surgery | Single arm of transplant |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | Single arm of transplant |
| in vitro-treated peripheral blood stem cell transplantation | Procedure or surgery | Single arm of transplant |
| total-body irradiation | Radiation | Single arm of transplant |
Primary outcome
Engraftment at 4 weeks post bone marrow transplantation through 100 days
Time frame: 100 days
4 secondary outcomes
Survival assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Time frame: 1 year
Disease-free survival and infection assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Time frame: 1 year
Graft-versus-host disease assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation
Time frame: 2 years
CD4 count in blood < 100/mm³ at 12 weeks
Time frame: 12 weeks
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 12 Nov 2012.
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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.
Morton J. Cowan, MD study chair
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anti-thymocyte globulin, therapeutic allogeneic lymphocytes and fludarabine phosphate in people with Congenital Amegakaryocytic Thrombocytopenia and Leukemia, run by University of California, San Francisco at 2 sites 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?
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 12 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does the primary outcome measure?
Engraftment at 4 weeks post bone marrow transplantation through 100 days (time frame: 100 days). 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 12 Nov 2012.