Severe Combined Immunodeficiency DiseasePhase 1/2MASCINCT00579137
Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
A Phase 1/2 study testing Campath -1H, Fludarabine and Anti-CD45 in people with Severe Combined Immunodeficiency Disease and Severe Primary Immunodeficiency Disorder, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype)… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T Cell Deficiency Disorder
- What is being tested?
- Campath -1H, Fludarabine and Anti-CD45
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Oct 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
- Patients with a diagnosis of: Severe combined immunodeficiency disease
- This includes patients whose SCID is characterized by gene specific mutations as well as patients with clinically severe combined immunodeficiency without a defined genetic cause in which the diagnosis will be determined by a combination of clinical course with lymphocyte quantification and function assays.
- OR
- Severe primary immunodeficiency disorder, including undefined T cell deficiency disorder, Wiskott-Aldrich syndrome, and other severe immunodeficiencies for which satisfactory conventional therapy does not exist.
- Availability of an HLA mismatched (up to one haplotype) family member or an HLA matched or mismatched (up to one antigen) unrelated donor.
- Creatinine < 2.5 x normal for age.
- Life expectancy greater than 6 weeks
- Lansky/Karnofsky greater than or equal to 70%
Who cannot join
- Patients with an HLA matched related donor
- 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
- HIV positive
- Pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease (SCID) And Other Primary Immunodeficiency Disorders
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched (up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them are rat IgG1 (immunoglobulin G1) 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. Campath 1H, Alemtuzumab, has been licensed 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 SCID, in whom the use of conventional chemotherapeutic agents for conditioning may produce or aggravate unacceptable and even lethal short 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 GvHD prophylaxis. Additional Graft versus Host Disease (GvHD) prophylaxis may be provided by administration of FK506.
Read the detailed description
Donor Stem Cell Processing for Mismatched Donors: Harvested peripheral blood stem cells will be enriched for CD34 cells using the CliniMACS CD34 Reagent system, according to Center for Cell and Gene Therapy (CAGT) SOPs.
Stem Cell Transplant Conditioning
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 i.v. q4h during the period of the course of the Campath and Anti-CD45 infusions.
Day
8 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
7 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
6 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
5 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
4 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
3 YTH 24/54 400ug/kg over 6 hr
2 YTH 24/54 400ug/kg over 6 hr
1 rest
0 Stem Cell Infusion
Campath 1H Infusion- Campath dose is weight based: for patients less than 15 killograms (kg) administer Campath 3 mg; for patients >15 kg to 30 kg administer Campath 5 mg; for patients > 30 kg administer Campath 10 mg. Campath will be dosed and administered as per CAGT SOP.
Anti-CD45- Infusion Anti-CD45 infusion will be administered according to CAGT SOPs. 3 ml of heparinized blood will be drawn 48 hr post Anti-CD45 to evaluate for free Anti-CD45 levels in the plasma. This estimation will be used to determine whether treatment with irradiated leukocytes is required before the bone marrow is infused.
GVHD Prophylaxis- 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 10 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 10 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. Patients who develop acute or chronic GVHD will be managed according to CAGT SOPs.
- Conditions
- Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T Cell Deficiency Disorder, Wiskott-Aldrick Syndrome
- Being tested
- Campath -1H, Fludarabine, Anti-CD45, Stem cell infusion
- Keywords
- Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T cell Deficiency Disorder, Wiskott-Aldrick Syndrome, Allogeneic stem cell transplant, Fludarabine, monoclonal antibodies
- Medical subject headings
- X-Linked Combined Immunodeficiency Diseases, Primary Immunodeficiency Diseases
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
Campath dose is weight based: for patients less than 15 kg the dose is 3 mg; for patients >15 kg to 30 kg the dose 5 mg; for patients > 30 kg the dose is 10 mg
FludarabineDrug
Also called Fludara
Given intravenous on Days -8,-7,-6,-5, and -4
Dose is 30 mg/m2
Anti-CD45Biological
Given intravenous over 6 hours on Days -5,-4,-3, and -2
Dose is 400 microgram/kg
Stem cell infusionProcedure or surgery
stem cells are infused on day 0
| Study group | Role | What they receive |
|---|---|---|
| Participants With SCID or Primary Immunodeficiency Disorder | Experimental | all patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45 Receives: Biological: Campath -1H; Drug: Fludarabine; Biological: Anti-CD45; 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
Measured: 100 Days
Secondary outcomes (3)
Patients Alive at 1 Year
Measured: 1 Year
Number of Patients With Grade III or IV Toxicity
Measured: 100 days
Number of Patients With Grade III to 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 posted21 Dec 2007 (estimated)
- Study startOct 2007
- Primary completionOct 2009
- Study completionOct 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 Severe Combined Immunodeficiency DiseaseStudies 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Robert Krance, Baylor College of Medicine
- Investigators
- Robert Krance, MD, Principal investigator, Baylor College of MedicineMalcolm Brenner, MD, Study chair, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00579137
- Sponsor's protocol ID
- 21123-MASCI
- Acronym
- MASCI
- Status last verified
- Jun 2013
- First submitted
- 19 Dec 2007
- Last updated
- 2 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD45 and Alemtuzumab Monoclonal Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Severe Combined Immunodeficiency Disease (SCID) And Other Primary Immunodeficiency Disorders
- ClinicalTrials.gov ID
- NCT00579137
- Acronym / sponsor ID
- MASCI / 21123-MASCI
- Conditions
- Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T Cell Deficiency Disorder, Wiskott-Aldrick Syndrome
- Keywords
- Severe Combined Immunodeficiency Disease, Severe Primary Immunodeficiency Disorder, Undefined T cell Deficiency Disorder, Wiskott-Aldrick Syndrome, Allogeneic stem cell transplant, Fludarabine, monoclonal antibodies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Oct 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 21 Dec 2007 (estimated)
- Results
- Posted 2 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to discover whether children with severe combined immunodeficiency disease (SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment other than stem cell transplantation (SCT) exists can be safely and effectively transplanted from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched (up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine are the sole conditioning agents. Three monoclonal antibodies will be used in combination. Two of them are rat IgG1 (immunoglobulin G1) 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. Campath 1H, Alemtuzumab, has been licensed 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 SCID, in whom the use of conventional chemotherapeutic agents for conditioning may produce or aggravate unacceptable and even lethal short 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 GvHD prophylaxis. Additional Graft versus Host Disease (GvHD) prophylaxis may be provided by administration of FK506.
Detailed description
Donor Stem Cell Processing for Mismatched Donors: Harvested peripheral blood stem cells will be enriched for CD34 cells using the CliniMACS CD34 Reagent system, according to Center for Cell and Gene Therapy (CAGT) SOPs.
Stem Cell Transplant Conditioning
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 i.v. q4h during the period of the course of the Campath and Anti-CD45 infusions.
Day
8 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
7 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
6 Campath 1H as per CAGT SOP Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
5 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
4 YTH 24/54 400ug/kg over 6 hr Fludarabine 10 kg or less: 1 mg/kg; > 10 kg: 30 mg/m2
3 YTH 24/54 400ug/kg over 6 hr
2 YTH 24/54 400ug/kg over 6 hr
1 rest
0 Stem Cell Infusion
Campath 1H Infusion- Campath dose is weight based: for patients less than 15 killograms (kg) administer Campath 3 mg; for patients >15 kg to 30 kg administer Campath 5 mg; for patients > 30 kg administer Campath 10 mg. Campath will be dosed and administered as per CAGT SOP.
Anti-CD45- Infusion Anti-CD45 infusion will be administered according to CAGT SOPs. 3 ml of heparinized blood will be drawn 48 hr post Anti-CD45 to evaluate for free Anti-CD45 levels in the plasma. This estimation will be used to determine whether treatment with irradiated leukocytes is required before the bone marrow is infused.
GVHD Prophylaxis- 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 10 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 10 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. Patients who develop acute or chronic GVHD will be managed according to CAGT SOPs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants With SCID or Primary Immunodeficiency Disorder | Experimental | Biological: Campath -1H, Drug: Fludarabine, Biological: Anti-CD45, Procedure: Stem cell infusionall patient will receive an allogeneic transplant with the following conditioning regimen Campath -1H, Fludarabine, Anti-CD45 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with a diagnosis of: Severe combined immunodeficiency disease
- This includes patients whose SCID is characterized by gene specific mutations as well as patients with clinically severe combined immunodeficiency without a defined genetic cause in which the diagnosis will be determined by a combination of clinical course with lymphocyte quantification and function assays.
- OR
- Severe primary immunodeficiency disorder, including undefined T cell deficiency disorder, Wiskott-Aldrich syndrome, and other severe immunodeficiencies for which satisfactory conventional therapy does not exist.
- Availability of an HLA mismatched (up to one haplotype) family member or an HLA matched or mismatched (up to one antigen) unrelated donor.
Key exclusion criteria (6 listed)
- Patients with an HLA matched related donor
- 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
- HIV positive
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 Campath dose is weight based: for patients less than 15 kg the dose is 3 mg; for patients >15 kg to 30 kg the dose 5 mg; for patients > 30 kg the dose is 10 mg | Biological | Participants With SCID or Primary Immunodeficiency Disorder |
| FludarabineAlso: FludaraGiven intravenous on Days -8,-7,-6,-5, and -4 Dose is 30 mg/m2 | Drug | Participants With SCID or Primary Immunodeficiency Disorder |
| Anti-CD45Given intravenous over 6 hours on Days -5,-4,-3, and -2 Dose is 400 microgram/kg | Biological | Participants With SCID or Primary Immunodeficiency Disorder |
| Stem cell infusionstem cells are infused on day 0 | Procedure or surgery | Participants With SCID or Primary Immunodeficiency Disorder |
Primary outcome
Number of Patients With Donor Engraftment
Time frame: 100 Days
3 secondary outcomes
Patients Alive at 1 Year
Time frame: 1 Year
Number of Patients With Grade III or IV Toxicity
Time frame: 100 days
Number of Patients With Grade III to 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 2 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Severe Combined Immunodeficiency Disease
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
RecruitingPhase 1/2
Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
X-linked Severe Combined Immunodeficiency (XSCID)
Not yet recruitingPhase 1/2
SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection
SCID, X-Linked
Not yet recruiting
Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)
Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)
Enrolling by invitationObservational study
Establishing Fibroblast-Derived Cell Lines From Skin Biopsies of Patients With Immunodeficiency or Immunodysregulation Disorders
Primary Immunodeficiency, DOCK8
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.
Robert Krance, MD principal investigator
Baylor College of Medicine
Malcolm Brenner, MD study chair
Baylor College of Medicine
1 site 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, Fludarabine and Anti-CD45 in people with Severe Combined Immunodeficiency Disease and Severe Primary Immunodeficiency Disorder, run by Baylor College of Medicine 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 8 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 2 Jul 2013. 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 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 2 Jul 2013). 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 2 Jul 2013.