Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies

NCT00145613 | Completed Phase 2

• 1 other identifier: REFSCT
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple therapies and elevated leukemic/tumor burden usually make these patients ineligible for the aggressive chemotherapy regimens required for conventional stem cell transplantation. Alternative options are needed. One type of treatment being explored is called haploidentical transplant. Conventional blood or bone marrow stem cell transplant involves destroying the patient's diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused into the patient where it migrates to the bone marrow space to begin generating new blood cells. The best type of donor is a sibling or unrelated donor with an identical immune system (HLA "match"). However, most patients do not have a matched sibling available and/or are unable to identify an acceptable unrelated donor through the registries in a timely manner. In addition, the aggressive treatment required to prepare the body for these types of transplants can be too toxic for these highly pretreated patients. Therefore doctors are investigating haploidentical transplant using stem cells from HLA partially matched family member donors. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD), and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the patient's (the host) body tissues are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for infection. However, the presence of T cells in the graft may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased cells. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution, graft integrity and GVM. In this study, patients were given a haploidentical graft engineered to with specific T cell parameter values using the CliniMACS system. A reduced intensity, preparative regimen was used to reduce regimen-related toxicity and mortality. The primary goal of this study is to evaluate overall survival in those who receive this study treatment.

Conditions

Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Secondary AML; Myelodysplastic Syndrome (MDS); Secondary MDS; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia (JMML); Paroxysmal Nocturnal Hemoglobinuria (PNH); Lymphoma, Non-Hodgkin; Hodgkin Disease

Keywords

Haploidentical stem cell transplant; High risk hematologic malignancies; Allogeneic stem cell transplant; Mismatched family member stem cell donor

Outcome Measures

Primary Outcomes (1)

• To ask in terms of one-year survival the efficacy of haploidentical stem cell transplantation in children with refractory hematological malignancies.

  July 2006

Study Arms (1)

1

OTHER

Procedure: Stem Cell Transplantation; Device: Miltenyi Biotec CliniMACS; Drug: Systemic chemotherapy and antibodies

Interventions

Stem Cell Transplantation PROCEDURE

An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.

1

Miltenyi Biotec CliniMACS DEVICE

stem cell selection device

1

Systemic chemotherapy and antibodies DRUG

Transplant recipients received a non-TBI based reduced intensity conditioning regimen consisting of OKT-3, Fludarabine Thiotepa, and Melphalan. Rituximab was administered within 24 hours of the transplant in an effort to prevent PTLPD. In addition to T-cell depletion of the haploidentical stem cell product, Mycophenolate mofetil was provided as prophylaxis for GVHD.

Also known as: Allogeneic stem cell transplant,, Mismatched family member donor stem cell transplant, Haploidentical donor stem cell transplant,, Reduced intensity conditioning regimen,, T-cell depletion donor stem cell processing

1

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acute lymphoblastic leukemia (ALL), must have isolated or combined bone marrow relapse or primary induction failure. Patients with extramedullary relapse are not eligible unless they have previously received a stem cell transplant
• Acute myeloid leukemia (AML) \>25% blasts in bone marrow
• Secondary AML
• Myelodysplastic syndrome (MDS)
• Secondary MDS
• Chronic myeloid leukemia (CML)
• Juvenile myelomonocytic leukemia (JMML)
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Non-Hodgkin's lymphoma (NHL)\*
• Hodgkin's Disease (HD)\*
• \*Patients with lymphomas must have failed standard non-cross reactive combination salvage chemotherapy with or without radiation therapy followed by autologous stem cell transplant or patients with chemo resistant disease
• If patient has had previous stem cell transplant, must not be no earlier than 3 months from previous date of transplant
• Patients with shortening fraction greater than or equal to 25%
• Patients with creatinine clearance greater than or equal to 40cc/min/1.73m\^2
• Patients with FVC greater than or equal to 40% of predicted, or pulse oximetry greater than or equal to 92% on room air

You may not qualify if:

• Patients with a known allergy to murine products
• (Female Patients) Patient is pregnant
• Female Patients) Patient is lactating

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Juvenile; Hemoglobinuria, Paroxysmal; Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

Stem Cell Transplantation; Antibodies

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gregory Hale, M.D.

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 5, 2005
• Study Start: June 1, 2003
• Primary Completion: July 1, 2006
• Study Completion: February 1, 2009
• Last Updated: February 13, 2009

Record last verified: 2009-02

Locations

US (1)