FANCONI ANEMIAPhase 1RAFHASNCT00586274
Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
A Phase 1 study testing CD34 selected haploidentical PBSCT, Fludarabine and T cell infusion in people with FANCONI ANEMIA, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
While stem cell transplantation has proven an effective means of treating a wide variety of diseases involving hematopoietic stem cells and their progeny, a shortage of donors has proved a major impediment to the widest application of the approach. Until recently, only MHC identical donors could be used with safety. Read more about this study
- Who is it for?
- Ages Up to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- FANCONI ANEMIA
- What is being tested?
- CD34 selected haploidentical PBSCT, Fludarabine and T cell infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2002to Jul 2009
- 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 Up to 64 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- At the time of eligibility for infusion of allodepleted T -cells patients must satisfy the criteria below:
- Patients with Fanconi anemia of all ages with severe aplasia (as evidenced by hypocellular bone marrow) who lack a suitable conventional related (i.e. 5/6 or 6/6 related) or 5/6 or 6/6 unrelated donor with at least 2 out of 3 of the following: a) ANC < 500/mm3, b) reticulocytes < 1% c) platelets < 50,000/mm3
- Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycinC or DEB prior to stem cell transplant. Have received a related haploidentical CD34-selected peripheral blood stem cell transplant with evidence of a full or partial hematopoietic donor chimerism (> 50%) in the peripheral blood.
Who cannot join
- Patients with a life expectancy (< 6 weeks) limited by diseases other than FA
- Patients with active GVHD > / = Grade II
- Patients with severe renal disease (i.e. creatinine greater than 3 X normal for age)
- Patients with severe hepatic disease (direct bilirubin greater than 3ug/dl or SGPT greater than 500ug/dl)
- Patients with a severe intercurrent infection
- Lansky scale < 60 or Karnofsky < 60
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: A Phase I Study Evaluating The Use Of Rft5-Dga To Deplete Alloreactive Cells For Patients With Fanconi Anemia After Haploidentical Stem Cell Transplantation
While stem cell transplantation has proven an effective means of treating a wide variety of diseases involving hematopoietic stem cells and their progeny, a shortage of donors has proved a major impediment to the widest application of the approach. Until recently, only MHC identical donors could be used with safety. Such donors were originally siblings or other closely related family members. Over the past decade, the growth of allogeneic donor panels has allowed transplantation with stem cells obtained from a volunteer donor panel.
While it is now possible to obtain HLA identical unrelated donor stem cells for approximately 75% of individuals of Northern European backgrounds, the situation for most other ethnic groups is much less satisfactory. Even when a matched donor can be found, the elapsed time between commencing the search and collecting the stem cells usually exceeds three months, a delay that may doom many of the neediest patients. Hence there has been considerable interest in making use of HLA haploidentical family donors. Most individuals have a first-degree relative who would be suitable for such protocols. Fanconi anemia (FA) is an autosomal recessive disorder characterized by the development of progressive aplastic anemia usually evident by about age seven years and often associated with various diverse congenital anomalies such as short stature, microcephaly, radial anomalies, horseshoe kidney, and cafe au lait spots.
This study will determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants with Fanconi anemia after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of Grade III/IV GVHD of < / = 25%.
Read the detailed description
Patients will have received a haplo-identical stem cell transplant on our on-going study "CD45 (YTH-24 and YTH-54) and CD52 (Campath 1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients with Fanconi Anemia" (H-9938 IND# 7233) and will become eligible to receive allodepleted T Cells following engraftment. What follows is a summary of the treatment plan including initial transplant phase as well as generation and infusion of allodepleted T cells.
Preparative Regimen for Patients with Fanconi Anemia:
The study will be open to patients who received a haploidentical PBSCT on the MAFIA protocol and for patients who failed to engraft and receive a second haploidentical transplants with alternate conditioning consisting of ATG, Fludarabine, TBI (450cGY single dose) and Cytoxan.
In Outline MAFIA conditioning (primary conditioning regimen)
Day 8 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 7 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 6 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
- 4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
- 3 YTH 24/54 400ug/kg over 6 hr
- 2 YTH 24/54 400ug/kg over 6 hr
- 1 Rest
- 0 CD34-selected PBSC infusion
Stem Cell Infusion: One day after the completion of pretransplant conditioning therapy (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs.
This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul.
Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg)
- Conditions
- FANCONI ANEMIA
- Being tested
- CD34 selected haploidentical PBSCT, Fludarabine, T cell infusion, Campath 1h, anti-CD45
- Keywords
- Stem Cell Transplant, Anemia, Fanconi
- Medical subject headings
- Fanconi Anemia, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34 selected haploidentical PBSCTProcedure or surgery
Infusion of CD34 selected haploidentical PBSCT
FludarabineDrug
day -8 through day -4 Fludarabine 30 mg/m^2
T cell infusionBiological
At least 30 days after the stem cell infusion, patients will be dosed with T cells. This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul.
Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg)
Campath 1hBiological
10 mg iv over 4 hours day-8 through day-6
anti-CD45Biological
anti-CD45 400 ug/kg over 6 hours day -5 through day -2
| Study group | Role | What they receive |
|---|---|---|
| CD34 selected haploidentical PBSCT | Experimental | CD34 selected haploidentical PBSCT Receives: Procedure: CD34 selected haploidentical PBSCT; Drug: Fludarabine; Biological: T cell infusion; Biological: Campath 1h; Biological: anti-CD45 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine # of donor lymphocytes that can be given to recipients of haplo-SCT with FA after depletion of recipient-reactive T lymphocytes by ex-vivo tx with a fixed dose of RFT5-dgA immunotoxin, and will result in Grade III/IV GVHD of < / = 25%.
Measured: 1 yr
Secondary outcomes (2)
To analyze immune reconstitution in these patients.
Measured: 1 yr
To measure their overall and disease free survival, at 100 days and at 1 year after transplant.
Measured: 1 yr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2008 (estimated)
- Study startMar 2002
- Primary completionJul 2009
- Study completionJul 2009
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FANCONI ANEMIAStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas, Southwestern Medical Center at Dallas, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Malcolm Brenner, Baylor College of Medicine
- Investigators
- Malcolm Brenner, MB, PhD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00586274
- Sponsor's protocol ID
- H-11428
- Acronym
- RAFHAS
- Status last verified
- Mar 2014
- First submitted
- 21 Dec 2007
- Last updated
- 4 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating The Use Of Rft5-Dga To Deplete Alloreactive Cells For Patients With Fanconi Anemia After Haploidentical Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00586274
- Acronym / sponsor ID
- RAFHAS / H-11428
- Conditions
- FANCONI ANEMIA
- Keywords
- Stem Cell Transplant, Anemia, Fanconi
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- University of Texas, Southwestern Medical Center at Dallas, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Mar 2002
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 4 Jan 2008 (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.
While stem cell transplantation has proven an effective means of treating a wide variety of diseases involving hematopoietic stem cells and their progeny, a shortage of donors has proved a major impediment to the widest application of the approach. Until recently, only MHC identical donors could be used with safety. Such donors were originally siblings or other closely related family members. Over the past decade, the growth of allogeneic donor panels has allowed transplantation with stem cells obtained from a volunteer donor panel.
While it is now possible to obtain HLA identical unrelated donor stem cells for approximately 75% of individuals of Northern European backgrounds, the situation for most other ethnic groups is much less satisfactory. Even when a matched donor can be found, the elapsed time between commencing the search and collecting the stem cells usually exceeds three months, a delay that may doom many of the neediest patients. Hence there has been considerable interest in making use of HLA haploidentical family donors. Most individuals have a first-degree relative who would be suitable for such protocols. Fanconi anemia (FA) is an autosomal recessive disorder characterized by the development of progressive aplastic anemia usually evident by about age seven years and often associated with various diverse congenital anomalies such as short stature, microcephaly, radial anomalies, horseshoe kidney, and cafe au lait spots.
This study will determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants with Fanconi anemia after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of Grade III/IV GVHD of < / = 25%.
Detailed description
Patients will have received a haplo-identical stem cell transplant on our on-going study "CD45 (YTH-24 and YTH-54) and CD52 (Campath 1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients with Fanconi Anemia" (H-9938 IND# 7233) and will become eligible to receive allodepleted T Cells following engraftment. What follows is a summary of the treatment plan including initial transplant phase as well as generation and infusion of allodepleted T cells.
Preparative Regimen for Patients with Fanconi Anemia:
The study will be open to patients who received a haploidentical PBSCT on the MAFIA protocol and for patients who failed to engraft and receive a second haploidentical transplants with alternate conditioning consisting of ATG, Fludarabine, TBI (450cGY single dose) and Cytoxan.
In Outline MAFIA conditioning (primary conditioning regimen)
Day 8 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 7 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 6 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
- 4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
- 3 YTH 24/54 400ug/kg over 6 hr
- 2 YTH 24/54 400ug/kg over 6 hr
- 1 Rest
- 0 CD34-selected PBSC infusion
Stem Cell Infusion: One day after the completion of pretransplant conditioning therapy (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs.
This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul.
Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD34 selected haploidentical PBSCT | Experimental | Procedure: CD34 selected haploidentical PBSCT, Drug: Fludarabine, Biological: T cell infusion, Biological: Campath 1h, Biological: anti-CD45CD34 selected haploidentical PBSCT |
Who may qualify
- Ages
- Up to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- At the time of eligibility for infusion of allodepleted T -cells patients must satisfy the criteria below:
- Patients with Fanconi anemia of all ages with severe aplasia (as evidenced by hypocellular bone marrow) who lack a suitable conventional related (i.e. 5/6 or 6/6 related) or 5/6 or 6/6 unrelated donor with at least 2 out of 3 of the following: a) ANC < 500/mm3, b) reticulocytes < 1% c) platelets < 50,000/mm3
- Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycinC or DEB prior to stem cell transplant. Have received a related haploidentical CD34-selected peripheral blood stem cell transplant with evidence of a full or partial hematopoietic donor chimerism (> 50%) in the peripheral blood.
Key exclusion criteria (6 listed)
- Patients with a life expectancy (< 6 weeks) limited by diseases other than FA
- Patients with active GVHD > / = Grade II
- Patients with severe renal disease (i.e. creatinine greater than 3 X normal for age)
- Patients with severe hepatic disease (direct bilirubin greater than 3ug/dl or SGPT greater than 500ug/dl)
- Patients with a severe intercurrent infection
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 selected haploidentical PBSCTInfusion of CD34 selected haploidentical PBSCT | Procedure or surgery | CD34 selected haploidentical PBSCT |
| Fludarabineday -8 through day -4 Fludarabine 30 mg/m^2 | Drug | CD34 selected haploidentical PBSCT |
| T cell infusionAt least 30 days after the stem cell infusion, patients will be dosed with T cells. This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are > 1000/ul. Dose level -1 (1 x 10^3 T cells/Kg); Dose level 1 (1 x 10^4 T cells/Kg); Dose level 2 (1 x 10^5 T cells/Kg); Dose level 3 (1 x 10^6 T cells/Kg); Dose level 4 (5 x 10^6 T cells/Kg) | Biological | CD34 selected haploidentical PBSCT |
| Campath 1h10 mg iv over 4 hours day-8 through day-6 | Biological | CD34 selected haploidentical PBSCT |
| anti-CD45anti-CD45 400 ug/kg over 6 hours day -5 through day -2 | Biological | CD34 selected haploidentical PBSCT |
Primary outcome
Determine # of donor lymphocytes that can be given to recipients of haplo-SCT with FA after depletion of recipient-reactive T lymphocytes by ex-vivo tx with a fixed dose of RFT5-dgA immunotoxin, and will result in Grade III/IV GVHD of < / = 25%.
Time frame: 1 yr
2 secondary outcomes
To analyze immune reconstitution in these patients.
Time frame: 1 yr
To measure their overall and disease free survival, at 100 days and at 1 year after transplant.
Time frame: 1 yr
Results and safety
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2014.
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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.
Malcolm Brenner, MB, PhD principal investigator
Baylor College of Medicine
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 CD34 selected haploidentical PBSCT, Fludarabine and T cell infusion in people with FANCONI ANEMIA, run by Baylor College of Medicine 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?
The sponsor lists 3 inclusion and 6 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: stopped early, as of the sponsor's last update on 4 Mar 2014. 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 was stopped early (reason given: Poor accrual). 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.
What does the primary outcome measure?
Determine # of donor lymphocytes that can be given to recipients of haplo-SCT with FA after depletion of recipient-reactive T lymphocytes by ex-vivo tx with a fixed dose of RFT5-dgA immunotoxin, and will result in Grade III/IV GVHD of < / = 25%. (time frame: 1 yr). 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 4 Mar 2014.