T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

NCT00368355 | Completed Phase 2 Results DMC

• 1 other identifier: H-8701-MOHEL
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

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 (BMT). 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.

Conditions

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)

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• Engraftment Rate After Transplant

  Percentage of participants with hematopoietic engraftment post-transplant. Engraftment is defined as the first day absolute neutrophil counts exceeded 0.5 X 10\^9/ml.

  28 days

Secondary Outcomes (4)

• Early Post BMT Toxicities

  100 Days

• Severe GVHD Rate

  100 Days

• Patients With Acute GVHD

  First 100 Days

• Patients With Chronic GVHD

  Up to 1 Year

Other Outcomes (2)

• Immune Reconstitution

  1 Year

• Length of Remission in Patients

  1 Year

Study Arms (2)

CLINIMACS Device

EXPERIMENTAL

Subjects will receive transplant conditioning with Ara-C, Cyclophosphamide, Campath-1H, Total Body Irradiation and will then receive T cell depleted stem cell infusion processed by the CLINIMACS Device

Drug: Ara-C; Drug: Cyclophosphamide; Biological: Campath-1H; Radiation: Total Body Irradiation; Procedure: Stem Cell Infusion

ISOLEX Device

EXPERIMENTAL

Subjects will receive transplant conditioning with Ara-C, Cyclophosphamide, Campath-1H, Total Body Irradiation and will then receive T cell depleted stem cell infusion processed by the ISOLEX Device

Drug: Ara-C; Drug: Cyclophosphamide; Biological: Campath-1H; Radiation: Total Body Irradiation; Procedure: Stem Cell Infusion

Interventions

Ara-C DRUG

day-8 through day-5 3 g/m2 q 12 hours

Also known as: cytarabine

CLINIMACS Device; ISOLEX Device

Cyclophosphamide DRUG

day-7 and day-6 45 mg/kg

Also known as: Cytoxan

CLINIMACS Device; ISOLEX Device

Campath-1H BIOLOGICAL

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

Also known as: Alemtuzumab

CLINIMACS Device; ISOLEX Device

Total Body Irradiation RADIATION

day-4 through day-1 175 cGy x 2 at 24 cGy/min

CLINIMACS Device; ISOLEX Device

Stem Cell Infusion PROCEDURE

Stem cells are infused on day 0

CLINIMACS Device; ISOLEX Device

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hosptial

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphohistiocytosis, Hemophagocytic; Lymphoproliferative Disorders

Interventions

Cytarabine; Cyclophosphamide; Alemtuzumab; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytosis, Non-Langerhans-Cell; Histiocytosis

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Dr. Robert A. Krance
• Organization: Baylor College of Medicine

rakrance@txch.org

832-824-4661

Study Officials

• Robert A. Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 21, 2005
• First Posted: August 24, 2006
• Study Start: April 1, 2000
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: January 21, 2020
• Results First Posted: January 21, 2020

Record last verified: 2020-01

Locations

US (2)