Crohn's DiseasePhase 1/2NCT01288053
Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease
A Phase 1/2 study testing Allogeneic Stem Cell Therapy in people with Crohn's Disease, run by Northwestern University at 1 site in United States.
Trial summary
Allogeneic transplantation has been a high-risk procedure, although non-myeloablative conditioning regimens (mini-transplantation) minimizes regimen related toxicity. The investigators, therefore, propose a phase I study of matched sibling allogeneic hematopoietic stem cell transplantation with non-myeloablative… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Allogeneic Stem Cell Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jun 2016
- 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 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age >18 years and less than age 45 years at time of pretransplant evaluation and,
- Ability to give informed consent.
- And either A or B A)An established clinical diagnosis of severe CD with disease onset before 16 years old (at least 71 genetic loci predispose to pediatric CD, Limbergen, JV. Annu. Rev. Genom. Human Genet. 2009; 10:89-116) that has failed therapy with prednisone, 5 ASA products and has failed an anti-TNF therapy. Failure is defined as a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
- B)Relapse after an autologous HSCT with a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
- 1. Donor must be an HLA 6 out of 6 matched sibling
Who cannot join
- HIV positive.
- History of coronary artery disease, or congestive heart failure.
- Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis
- Positive pregnancy test, lactation, inability or unwillingness to pursue effective means of birth control, failure to accept or comprehend irreversible sterility as a side effect of therapy.
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
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- FEV 1/FVC < 50% of predicted, DLCO < 50% of predicted.
- Resting LVEF < 50%.
- Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal, unless the abnormalities are secondary to Crohn's disease.
- Serum creatinine > 2.0 mg/dl.
- Platelet count less than 100,000/ul, ANC less than 1500/ul.
- Patients presenting with intestinal perforation or toxic megacolon, or a suppurative problem that will require urgent surgery. In addition, the patient may not have any active infection. The presence of intestinal stomas does not exclude the patient from study.
- Pre-study peripheral blood counts must include a platelet count greater than 100,000/ul and an absolute neutrophil count greater than 1500/ul.
- Creatinine clearance more than 20% below lower limit of normal for age and sex.
- Short gut syndrome.
- Donor eligibility
- Physiologic age > 50 years old or <18 years old
- HIV positive
- Active ischemic heart disease or heart failure
- Acute or chronic active hepatitis
- Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the donor to tolerate stem cell collection
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
- Positive pregnancy test
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul
- Donor has history of Crohn's or ulcerative colitis
Trial locations and contacts
1 site in 1 country.
About this study
Allogeneic transplantation has been a high-risk procedure, although non-myeloablative conditioning regimens (mini-transplantation) minimizes regimen related toxicity. The investigators, therefore, propose a phase I study of matched sibling allogeneic hematopoietic stem cell transplantation with non-myeloablative conditioning. In addition, graft versus host disease (GVHD) will be virtually eliminated by CAMPATH that removes donor T cells from the graft.
The goal is to assess the toxicity/efficacy (phase I) of allogeneic non-myeloablative hematopoietic stem cell transplantation for high-risk Crohn's disease. In simplistic terms, this protocol is designed to ablate an aberrant immune system and then, similar to the use of marrow transplants for immunodeficient patients, reconstitute a new immune system with lymphocyte depleted marrow.
Read the detailed description
PBSC will be mobilized with G-CSF 10 mcg/kg/day (dose may be adjusted down to 5 mcg/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4 or 5. Leukapheresis may be repeated up to three consecutive days.
Cyclophosphamide 60 mg/kg/day x 2 days will be given IV over 1 hour in 500 cc of normal saline.
Dosage should be based on the lesser of adjusted body weight or actual weight. Mesna 50mg/day x 2 days will be given IV over 24 hours
CAMPATH-1H 30mg/day x 2 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with Solumedrol 1g IV, Acetaminophen 650mg \& benadryl 50mg PO/IV will be given 30-60min before infusion. Also while on CAMPATH, Chlorphenamine 4 mg PO TID, Singular 10 mg PO daily, Pepcid 40 mg PO BID and Claritin 10 mg PO daily will be given, adjusted as needed. These medications can be repeated or changed as needed.
Fludarabine 30mg/m2 daily for 3 days (no dose adjustment) will be given IV over 30 minutes in 100 cc normal saline.
Hydration approximately 150ml/hr should begin 2 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose. Daily weights will be obtained. Amount of fluid can be modified based on patient's fluid status.
G-CSF will be continued until absolute neutrophil count reaches at least 1,000/ul.
Cyclosporin will be started on day -2 at 200 mg po BID and adjusted by HPLC levels to between 150 - 250 or by toxicity (e.g., tremor, renal insufficiency, TTP, etc.). CSA will be continued for 30 days unless stopped for toxicity or needed to maintain donor engraftment.
Cyclosporine and MMF guidelines dosage and duration can be modified according to investigators discretion based on side effects, renal function, CBC and GVHD status.
- Conditions
- Crohn's Disease
- Being tested
- Allogeneic Stem Cell Therapy
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Stem Cell TherapyBiological
Donor stem cells will be given to subject diagnosed with Crohn's disease
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Stem Cell Therapy | Experimental | Allogeneic Stem Cell Therapy will be performed after conditioning Receives: Biological: Allogeneic Stem Cell Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
The number of participants who survived treatment
Measured: Up to five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2011 (estimated)
- Study startJan 2010
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: No participant enrolled more than two years. No plan to continue study.
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 Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01288053
- Sponsor's protocol ID
- DIADCDAllo2005
- Status last verified
- Aug 2018
- First submitted
- 27 Jan 2011
- Last updated
- 6 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Refractory Crohn's Disease
- ClinicalTrials.gov ID
- NCT01288053
- Acronym / sponsor ID
- DIADCDAllo2005
- Conditions
- Crohn's Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No participant enrolled more than two years. No plan to continue study.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 2 Feb 2011 (estimated)
- Results
- Posted 6 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Allogeneic transplantation has been a high-risk procedure, although non-myeloablative conditioning regimens (mini-transplantation) minimizes regimen related toxicity. The investigators, therefore, propose a phase I study of matched sibling allogeneic hematopoietic stem cell transplantation with non-myeloablative conditioning. In addition, graft versus host disease (GVHD) will be virtually eliminated by CAMPATH that removes donor T cells from the graft.
The goal is to assess the toxicity/efficacy (phase I) of allogeneic non-myeloablative hematopoietic stem cell transplantation for high-risk Crohn's disease. In simplistic terms, this protocol is designed to ablate an aberrant immune system and then, similar to the use of marrow transplants for immunodeficient patients, reconstitute a new immune system with lymphocyte depleted marrow.
Detailed description
PBSC will be mobilized with G-CSF 10 mcg/kg/day (dose may be adjusted down to 5 mcg/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4 or 5. Leukapheresis may be repeated up to three consecutive days.
Cyclophosphamide 60 mg/kg/day x 2 days will be given IV over 1 hour in 500 cc of normal saline.
Dosage should be based on the lesser of adjusted body weight or actual weight. Mesna 50mg/day x 2 days will be given IV over 24 hours
CAMPATH-1H 30mg/day x 2 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with Solumedrol 1g IV, Acetaminophen 650mg \& benadryl 50mg PO/IV will be given 30-60min before infusion. Also while on CAMPATH, Chlorphenamine 4 mg PO TID, Singular 10 mg PO daily, Pepcid 40 mg PO BID and Claritin 10 mg PO daily will be given, adjusted as needed. These medications can be repeated or changed as needed.
Fludarabine 30mg/m2 daily for 3 days (no dose adjustment) will be given IV over 30 minutes in 100 cc normal saline.
Hydration approximately 150ml/hr should begin 2 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose. Daily weights will be obtained. Amount of fluid can be modified based on patient's fluid status.
G-CSF will be continued until absolute neutrophil count reaches at least 1,000/ul.
Cyclosporin will be started on day -2 at 200 mg po BID and adjusted by HPLC levels to between 150 - 250 or by toxicity (e.g., tremor, renal insufficiency, TTP, etc.). CSA will be continued for 30 days unless stopped for toxicity or needed to maintain donor engraftment.
Cyclosporine and MMF guidelines dosage and duration can be modified according to investigators discretion based on side effects, renal function, CBC and GVHD status.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Stem Cell Therapy | Experimental | Biological: Allogeneic Stem Cell TherapyAllogeneic Stem Cell Therapy will be performed after conditioning |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age >18 years and less than age 45 years at time of pretransplant evaluation and,
- Ability to give informed consent.
- And either A or B A)An established clinical diagnosis of severe CD with disease onset before 16 years old (at least 71 genetic loci predispose to pediatric CD, Limbergen, JV. Annu. Rev. Genom. Human Genet. 2009; 10:89-116) that has failed therapy with prednisone, 5 ASA products and has failed an anti-TNF therapy. Failure is defined as a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
- B)Relapse after an autologous HSCT with a CDAI (appendix A) 250-400 or a Craig Severity Score that is > 17 (appendix C).
- 1. Donor must be an HLA 6 out of 6 matched sibling
Key exclusion criteria (26 listed)
- HIV positive.
- History of coronary artery disease, or congestive heart failure.
- Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis
- Positive pregnancy test, lactation, inability or unwillingness to pursue effective means of birth control, failure to accept or comprehend irreversible sterility as a side effect of therapy.
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 |
|---|---|---|
| Allogeneic Stem Cell TherapyDonor stem cells will be given to subject diagnosed with Crohn's disease | Biological | Allogeneic Stem Cell Therapy |
Primary outcome
Survival
Time frame: Up to five years
The number of participants who survived treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Richard Burt, MD principal investigator
Northwestern University
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 Allogeneic Stem Cell Therapy in people with Crohn's Disease, run by Northwestern University 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 5 inclusion and 26 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 6 Aug 2018. 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 6 Aug 2018). 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?
Survival (time frame: Up to five years). 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 6 Aug 2018.