T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts (MOHEL)
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Purpose
Subjects are being asked to participate in this study because treatment of their disease requires them to receive a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation. Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) and the subject's disease is considered rapidly progressive and does not permit enough time to identify another donor (like someone from a registry list that is not their relative). We have, however, identified a close relative of the subject's whose stem cells are not a perfect match, but can be used. However, with this type of donor, there is typically an increased risk of developing graft-versus-host disease (GVHD), a high rate of transplant failure, and a longer delay in the recovery of the immune system.
GVHD is a serious and sometimes fatal side effect of stem cell transplant. GVHD occurs when the new donor cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, liver, and intestines. The number of occurrences and harshness of severe GVHD depends on several factors, including the degree of genetic differences between the donor and recipient, the intensity of the pre-treatment conditioning regimen, the quantity of transplanted cells, and the recipient's age. In recipients of mismatched family member or matched unrelated donor stem cell transplants, there is a greater risk of GVHD so that 70-90% of recipients of unchanged marrow will develop severe GVHD which could include symptoms such as marked diarrhea, liver failure, or even death.
In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, we would like to specially treat the donor's blood cells to remove cells that are most likely to attack the patient's tissues. This will occur in combination with intense conditioning treatment that the patient will receive before the transplant.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Lymphoblastic Leukemia Non Hodgkins Lymphoma Myelodysplastic Syndrome Acute Myeloid Leukemia Chronic Myelogenous Leukemia Hemophagocytic Lymphohistiocytosis (HLH) Familial Hemophagocytic Lymphohistiocytosis (FLH) Viral-associated Hemophagocytic Syndrome (VAHS) X-linked Lymphoproliferative Disease (XLP) |
Drug: Ara-C Drug: Cyclophosphamide Biological: Campath-1H Radiation: Total Body Irradiation Procedure: Stem Cell Infusion |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | CD-34 Selection for Ex-vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Receiving Intensive Conditioning |
- Number of patients with severe acute GVHD [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Number of patients with engraftment [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Number of patients with severe Chronic GVHD [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Assessment of immune reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 87 |
| Study Start Date: | April 2000 |
| Estimated Study Completion Date: | December 2018 |
| Estimated Primary Completion Date: | December 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: CLINIMACS Device
Subjects will receive transplant conditioning with Ara-C, Cyclophosphamide, Campath-1H, Total Body Irradiation and will then receive T cell depleted stem cells processed by the CLINIMACS Device
|
Drug: Ara-C
day-8 through day-5 3 g/m2 q 12 hours Other Name: cytarabine
Drug: Cyclophosphamide
day-7 and day-6 45 mg/kg Other Name: Cytoxan
Biological: Campath-1H
day-3 through day-1 Dosing for children: 5 - 15kg : 3mg IV in 30ml NS 15.1 - 30kg : 5mg IV in 50ml NS >30 kg : 10mg IV in 100ml NS Adults will receive 10mg IV in 100ml NS Other Name: Alemtuzumab
Radiation: Total Body Irradiation
day-4 through day-1 175 cGy x 2 at 24 cGy/min Stem cells are infused on day 0
|
|
Experimental: ISOLEX Device
Subjects will receive transplant conditioning with Ara-C, Cyclophosphamide, Campath-1H, Total Body Irradiation and will then receive T cell depleted stem cells processed by the ISOLEX Device
|
Drug: Ara-C
day-8 through day-5 3 g/m2 q 12 hours Other Name: cytarabine
Drug: Cyclophosphamide
day-7 and day-6 45 mg/kg Other Name: Cytoxan
Biological: Campath-1H
day-3 through day-1 Dosing for children: 5 - 15kg : 3mg IV in 30ml NS 15.1 - 30kg : 5mg IV in 50ml NS >30 kg : 10mg IV in 100ml NS Adults will receive 10mg IV in 100ml NS Other Name: Alemtuzumab
Radiation: Total Body Irradiation
day-4 through day-1 175 cGy x 2 at 24 cGy/min Stem cells are infused on day 0
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | up to 55 Years (Child, Adult) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
- Lack of suitable conventional donor (i.e. 5/6 or 6/6 related or 5/6 or 6/6 unrelated donor) or presence of a rapidly progressive disease not permitting time to identify an unrelated donor
- Age less than or equal to 55 years of age
- Patients with high risk ALL in CR1 or ALL or high grade (stage III or IV) NHL after first relapse or with primary refractory disease or minimal residual diseases.
- Myelodysplastic syndrome
- Patients with high risk AML in CR1 (complement receptor 1) or after first relapse or with primary refractory disease or minimal residual disease.
- CML
- Hemophagocytic lymphohistiocytosis (HLH), familial hemophagocytic lymphohistiocytosis (FLH), viral-associated hemophagocytic syndrome (VAHS), X-linked lymphoproliferative disease (XLP), Severe chronic active Epstein Barr virus infection (SCAEBV) with predilection for T- or NK-cell malignancy
- Donor cells should be collected and frozen before conditioning starts
EXCLUSION CRITERIA:
- Patients with a life expectancy (< / = 6 weeks) limited by diseases other than leukemia
- Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction < 25%)
- Patients with severe renal disease (i.e., creatinine clearance less than 40 cc/1.73 m^2)
- Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted)
- Patients with severe hepatic disease (direct bilirubin greater than 3 ug/dl or SGPT (serum glutamic-pyruvic transaminase) greater than 500 ug/dl)
- Patients with severe personality disorder or mental illness
- Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation
- Patients with documented HIV positivity
'High risk' ALL or AML refers to those acute leukemias identified by the presence of specific biologic features, which predict high likelihood of failure to conventional chemotherapy. As biologic features of high risk disease evolve with improvement of conventional chemotherapy, it is not practical to define this indication with any further specificity. Therefore, high risk AML/ALL will be determined by the primary physician.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00368355
| Contact: Robert A. Krance, MD | 832-824-4661 | rakrance@txch.org | |
| Contact: Marlen Dinu | 832-824-4881 | mxdinu@txch.org |
| United States, Texas | |
| Houston Methodist Hospital | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Robert A. Krance, MD 832-824-4661 rakrance@txch.org | |
| Contact: Marlen Dinu 832-824-4881 mxdinu@txch.org | |
| Texas Children's Hosptial | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Robert A. Krance, MD 832-824-4661 rakrance@txch.org | |
| Contact: Marlen Dinu 832-824-4881 mxdinu@txch.org | |
| Principal Investigator: | Robert A. Krance, MD | Baylor College of Medicine |
More Information
| Responsible Party: | Robert Krance, Professor, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00368355 History of Changes |
| Other Study ID Numbers: | H-8701-MOHEL MOHEL |
| Study First Received: | September 21, 2005 |
| Last Updated: | June 2, 2016 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Baylor College of Medicine:
|
haploidenticalstem cell transplant acute lymphoblastic leukemia Non Hodgkins Lymphoma Myelodysplastic Syndrome Acute myeloid leukemia |
Chronic myelogenous leukemia Hemophagocytic lymphohistiocytosis (HLH) Familial hemophagocytic lymphohistiocytosis (FLH) Viral-associated hemophagocytic syndrome (VAHS) X-linked lymphoproliferative disease (XLP) |
Additional relevant MeSH terms:
|
Leukemia Syndrome Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Lymphoma, Non-Hodgkin Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphohistiocytosis, Hemophagocytic Lymphoproliferative Disorders Neoplasms by Histologic Type Neoplasms Disease |
Pathologic Processes Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Lymphoma Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Myeloproliferative Disorders Histiocytosis, Non-Langerhans-Cell Histiocytosis Cyclophosphamide Alemtuzumab Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on September 28, 2016