Allogeneic hematopoietic cell transplantation for patients with treatment-refractory Crohn’s Disease: A phase 2 study


University of Washington and Fred Hutchinson Cancer Research Center
1100 Fairview Avenue North
Seattle, WA, 98109

Study Objective:

The primary objective is to evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation as treatment for severe, refractory Crohn’s Disease. The hypothesis to be tested: Allogeneic transplantation can achieve complete, sustained remissions in patients with refractory Crohn’s Disease, and can be done safely.

Disease Information:

Crohn’s Disease

Severe

Study Details:

Drug Comparison:

Conventional immunosuppressive or immunomodulatory therapy for CD may not be adequate for achieving and maintaining remission in patients with severe CD. These patients experience ongoing medical problems and frequent surgeries putting them at risk for short bowel syndrome and ongoing need for anti-inflammatory durgs that pose a risk of infection. There is a strong genetic factor predisposing patients to severe CD (Am J Human Genetics 2013). Sustained remissions have been observed in CD patients who received bone marrow transplants (Gastroenterology 1998; Transplantation 2003).

This study is a prospective, open-label, single-arm Phase II clinical trial evaluating allogeneic bone marrow transplantation for the treatment of refractory CD. Eligible subjects will have active CD that has responded poorly to standard therapy and for whom an eligible donor has been identified who can be either a brother or sister, or an unrelated donor. A patient’s own blood cells will be collected and stored, to be used in the event of graft rejection after transplant. Patients will receive a reduced intensity conditioning regimen of immune suppressive drugs to prepare them to receive donor cells. Bone marrow will be used as the graft source. Subjects will be extensively studied for safety and efficacy utilizing clinical assessments, laboratory testing, endoscopy of the gastrointestinal tract, and histologic examination of tissue samples. Tissue and blood samples will be collected and archived for future studies and evaluation of immune reconstitution at predefined intervals. Well-validated scoring systems will be used at baseline and at intervals after transplant, specifically for activity of CD, quality of life, and endoscopic extent of inflammatory lesions.

Possible Risks and Side Effects:

The allogeneic transplant process starts with therapy to weaken a patient’s immune system so that it will accept immune cells from another person. After that other person’s bone marrow cells are given to the patient, immune suppressive medicines are given to prevent the new cells from being rejected and to stop those cells from damaging the patient. After the new donor cells start to work, blood counts will rise and the new immune system will start to grow. During this time, there is a risk of infection. Antibiotics and anti-viral drugs will be given to prevent infection. When the new donor cells are well-established, immune suppressive medicines are discontinued.

Allogeneic bone marrow transplantation carries risk, including death, because of infection, the rejection of donor cells, and those cells attacking a patient’s tissues (called graft-versus-host disease). In our Crohn’s Allogeneic Transplant Study (CATS) protocol, specific techniques will be employed to lower the risk of fatal complications, namely exclusion of patients with diseases of the heart, lungs, and kidneys, for example; medical co-morbidities; optimal prophylaxis against Graft-versus-Host Disease; optimal infection prophylaxis; and the storage of a patient’s own cells before the start of conditioning therapy, to be reinfused in the event of graft-rejection after transplant. The possible benefit is the disappearance of Crohn’s Disease.

Explanation of Participation:

This study will enroll 12 subjects over a 2-year period. The active treatment period will be approximately 3-4 months after transplant (day 0). Evaluations of CD status and safety endpoints are at 1 month, 3 months, and 12 months then annually up to 60 months (5 years). Subjects are expected to be in study for 5 years. The primary endpoint will be survival with no signs of active CD at 1 year after transplant.

We will select patients with severe Crohn’s Disease and active inflammation despite the best medical and surgical treatments. These patients must be healthy enough to undergo a transplantation procedure. They cannot have an active infection, and their heart, lungs, kidneys, and liver cannot be failing. A screening questionnaire is embedded within the CATS website; we review responses to this questionnaire, and contact all those who responded. If preliminary screening suggests that a patient might be eligible, we invite such a patient to come to Seattle to consult with the study investigators. If patients are found to be eligible and willing to proceed, we will contact their medical insurance company for approval of coverage for the transplant procedure, which will take place in Seattle. Once we have this approval, we will begin a search for a matched donor, someone who will donate bone marrow cells for the transplant.

Observation Period:
Patients will be formally evaluated for Crohn’s activity at 100 days after transplant, and yearly after that for 5 years.

Participant Criteria:

Adult (18+)

Female, Male

Patient Criteria:

Summary of INCLUSION criteria:

  1. A diagnosis of CD established by referring physician(s).
  2. A bad prognosis, documented by persistent signs and symptoms of CD that have failed to respond satisfactorily to medical and surgical therapies in the past.
  3. Endoscopic and histologic evidence of active intestinal inflammation consistent with CD.
  4. Severe CD as defined by one of the following:
    a. Crohn’s Disease Activity Index ≥250
    b. Need for total parenteral nutrition to maintain weight
    c. Recurrent intestinal inflammation caused by CD following surgical resection
  5. Identification of an HLA-matched hematopoietic cell donor.
  6. Age from 18 through 60 years.

Summary of EXCLUSION criteria:

  1. Diagnosis of CD in a patient caused by underlying immune deficiency disorder, such as SCID, IPEX, and others
  2. A current complication of CD that would jeopardize survival after hematopoietic cell transplantation.
  3. History of serious infection or heart, lung, or kidney disorder or another serious disease other than CD.
  4. Pregnancy.
  5. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following transplant.
  6. History of smoking either tobacco or other herbal products in the last 6 months.
  7. History of cancer, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ.

 Additional Information:

This website contains information for physicians and patients, including contact information: www.CATS-FHCRC.org. Embedded within the website is a questionnaire that is used as a screening tool for eligibility.

Center Name:

University of Washington and Fred Hutchinson Cancer Research Center

Site Location:

1100 Fairview Avenue North
Seattle, WA, 98109

Principal Investigator:

George B. McDonald, MD

Site Coordinator(s):

Christine Kane
Phone: (206) 667.2287
CATS@fhcrc.org

Bernadette McLaughlin, RN
Phone: (206) 667.2287
CATS@fhcrc.org

Study sponsor

Study sponsor