Fanconi AnemiaPhase 1/2MafiaNCT00590460
Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
A Phase 1/2 study testing CAMPATH-1H, Anti-CD45 and Fludarabine in people with Fanconi Anemia and Severe Aplastic Anemia, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with Human Leukocyte Antigen (HLA) mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Fanconi Anemia, Severe Aplastic Anemia
- What is being tested?
- CAMPATH-1H, Anti-CD45 and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2001to Sep 2009
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of Fanconi Anemia or other suspected DNA breakage/chromosomal instability syndromes, such as dyskeratosis congenita or Nijmegen breakage syndrome of all ages are eligible.
- Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycin C or DEB or clinical evidence of other DNA breakage/chromosomal instability syndrome as determined by genetic testing or clinical diagnosis by a geneticist
- Severe aplasia anemia as evidenced by a hypocellular bone marrow and at least 1 of the 3 criteria below: ANC < 500/mm3 Hemoglobin < 10 gm/dl with reticulocyte count < 1% Platelet count < 50,000/mm3
- Availability of an HLA matched or mismatched (up to one haplotype) family member who has been documented not to have Fanconi anemia or of an unrelated HLA matched stem cell donor. Fully matched is defined at 6/6 match by high resolution DR based DNA typing.
- Life expectancy greater than 6 weeks limited by diseases other than FA
- Creatinine 2X normal for age or less
- Karnofsky score 70% or more
Who cannot join
- Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%).
- Patients with known allergy to rat serum products.
- Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation.
- Patients with severe personality disorder or mental illness.
- Patients with documented HIV positivity.
- Pregnant
- NOTE: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA Reviewer.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: 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
The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with Human Leukocyte Antigen (HLA) mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole conditioning agents (patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen). Three monoclonal antibodies (MAb) will be used in combination. Two of them, YTH 24 and YTH 54 are rat antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. This MAb has been widely used to treat B cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia, in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial graft versus host disease (GvHD) prophylaxis. Additional GvHD prophylaxis will be provided by administration of the medication FK506.
Read the detailed description
If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftment/rejection is followed by failure to undergo autologous reconstitution.
For HLA Mismatched donors, harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system.
Fludarabine will be given as 5 daily intravenous infusions. Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion.
Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -6 Campath 1H as per CAGT SOP 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 -0 Stem Cell Infusion
GVHD prophylaxis will be achieved through positive selection for CD34 resulting in > 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GvHD after haploidentical transplants if recipients receive stem cell populations containing <5 x 10e4 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo.
- Conditions
- Fanconi Anemia, Severe Aplastic Anemia
- Being tested
- CAMPATH-1H, Anti-CD45, Fludarabine, Stem cell infusion
- Keywords
- Allogeneic Stem Cell Transplant, Fanconi Anemia, Severe Aplastic Anemia, fludarabine, campath, anti-CD45
- Medical subject headings
- Fanconi Anemia, Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAMPATH-1HBiological
Also called Alemtuzumab
Given intravenous on days -8, -7, and -6
Anti-CD45Biological
Given intravenous on days -5, -4, -3 and -2
dose is 400 micrograms/kg
FludarabineDrug
Given intravenous on days -8, -7, -6, -5 and -4
Dose is 30 mg/m2
Stem cell infusionProcedure or surgery
Stem cells are infused on day 0
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study: Stem Cell Transplant | Experimental | CAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion Receives: Biological: CAMPATH-1H; Biological: Anti-CD45; Drug: Fludarabine; Procedure: Stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Donor Engraftment
Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation
Measured: 100 Days
Secondary outcomes (9)
Number of Patients With Graft Failure
Graft failure is defined as engraftment of less than 65% of donor cells 100 days after transplantation.
Measured: 100 days
Patients With Treated Related Death
Number of patients with treated related death
Measured: 100 days
Days to Absolute Neutrophil Count (ANC) of 500/mm3
Number of days to Absolute neutrophil count (ANC) of 500/mm3
Measured: 30 Days
Days to Platelet Count of 20,000/mm3 Without Transfusions
Number of days to Platelet count of 20,000 / mm3 without transfusions
Measured: 30 Days
Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)
Number of patients with grade II - IV acute Graft versus Host Disease (GVHD)
Measured: 100 days
Number of Patients Alive at 1 Year Post Transplant
Number of patients alive at 1 year post allogeneic stem cell transplant
Measured: 1 year
Patients With Limited Chronic GVHD From Day 100 to 365
Number of patients with limited chronic GVHD from day 100 to 365
Measured: 365 days
Patients With Extensive Chronic GVHD From Day 100 to 365
Number of patients with extensive chronic GVHD from day 100 to 365.
Measured: 365 days
Patients With Grade III - IV Acute GVHD
Number of patients with Grade III-IV acute GVHD
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2008 (estimated)
- Study startJul 2001
- Primary completionSep 2009
- Study completionSep 2009
Why it stopped: slow accrual
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 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Malcolm Brenner, Baylor College of Medicine
- Investigators
- Malcolm Brenner, M.B., Ph.D.,, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590460
- Sponsor's protocol ID
- H-9938
- Acronym
- Mafia
- Status last verified
- Apr 2018
- First submitted
- 26 Dec 2007
- Last updated
- 24 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00590460
- Acronym / sponsor ID
- Mafia / H-9938
- Conditions
- Fanconi Anemia, Severe Aplastic Anemia
- Keywords
- Allogeneic Stem Cell Transplant, Fanconi Anemia, Severe Aplastic Anemia, fludarabine, campath, anti-CD45
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Jul 2001
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 10 Jan 2008 (estimated)
- Results
- Posted 9 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with Human Leukocyte Antigen (HLA) mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole conditioning agents (patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen). Three monoclonal antibodies (MAb) will be used in combination. Two of them, YTH 24 and YTH 54 are rat antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. This MAb has been widely used to treat B cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia, in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial graft versus host disease (GvHD) prophylaxis. Additional GvHD prophylaxis will be provided by administration of the medication FK506.
Detailed description
If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftment/rejection is followed by failure to undergo autologous reconstitution.
For HLA Mismatched donors, harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system.
Fludarabine will be given as 5 daily intravenous infusions. Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion.
Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -6 Campath 1H as per CAGT SOP 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 -0 Stem Cell Infusion
GVHD prophylaxis will be achieved through positive selection for CD34 resulting in > 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GvHD after haploidentical transplants if recipients receive stem cell populations containing <5 x 10e4 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo.
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 Study: Stem Cell Transplant | Experimental | Biological: CAMPATH-1H, Biological: Anti-CD45, Drug: Fludarabine, Procedure: Stem cell infusionCAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of Fanconi Anemia or other suspected DNA breakage/chromosomal instability syndromes, such as dyskeratosis congenita or Nijmegen breakage syndrome of all ages are eligible.
- Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycin C or DEB or clinical evidence of other DNA breakage/chromosomal instability syndrome as determined by genetic testing or clinical diagnosis by a geneticist
- Severe aplasia anemia as evidenced by a hypocellular bone marrow and at least 1 of the 3 criteria below: ANC < 500/mm3 Hemoglobin < 10 gm/dl with reticulocyte count < 1% Platelet count < 50,000/mm3
- Availability of an HLA matched or mismatched (up to one haplotype) family member who has been documented not to have Fanconi anemia or of an unrelated HLA matched stem cell donor. Fully matched is defined at 6/6 match by high resolution DR based DNA typing.
- Life expectancy greater than 6 weeks limited by diseases other than FA
Key exclusion criteria (7 listed)
- Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%).
- Patients with known allergy to rat serum products.
- Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation.
- Patients with severe personality disorder or mental illness.
- Patients with documented HIV positivity.
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 |
|---|---|---|
| CAMPATH-1HAlso: AlemtuzumabGiven intravenous on days -8, -7, and -6 | Biological | Single Arm Study: Stem Cell Transplant |
| Anti-CD45Given intravenous on days -5, -4, -3 and -2 dose is 400 micrograms/kg | Biological | Single Arm Study: Stem Cell Transplant |
| FludarabineGiven intravenous on days -8, -7, -6, -5 and -4 Dose is 30 mg/m2 | Drug | Single Arm Study: Stem Cell Transplant |
| Stem cell infusionStem cells are infused on day 0 | Procedure or surgery | Single Arm Study: Stem Cell Transplant |
Primary outcome
Number of Patients With Donor Engraftment
Time frame: 100 Days
Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation
9 secondary outcomes
Number of Patients With Graft Failure
Time frame: 100 days
Patients With Treated Related Death
Time frame: 100 days
Days to Absolute Neutrophil Count (ANC) of 500/mm3
Time frame: 30 Days
Days to Platelet Count of 20,000/mm3 Without Transfusions
Time frame: 30 Days
Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)
Time frame: 100 days
Number of Patients Alive at 1 Year Post Transplant
Time frame: 1 year
Patients With Limited Chronic GVHD From Day 100 to 365
Time frame: 365 days
Patients With Extensive Chronic GVHD From Day 100 to 365
Time frame: 365 days
Patients With Grade III - IV Acute GVHD
Time frame: 100 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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, M.B., Ph.D., 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 1/2 study testing CAMPATH-1H, Anti-CD45 and Fludarabine in people with Fanconi Anemia and Severe Aplastic 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 7 inclusion and 7 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 24 May 2018. 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 combined 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.
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 9 Aug 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?
Number of Patients With Donor Engraftment (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 24 May 2018.