Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies

This study has been completed.
Sponsor:
Information provided by:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00145613
First received: September 1, 2005
Last updated: February 12, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
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
Procedure: Stem Cell Transplantation
Device: Miltenyi Biotec CliniMACS
Drug: Systemic chemotherapy and antibodies
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Haploidentical Stem Cell Transplantation Utilizing T-Cell Depletion as Therapy for Patients With Refractory Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • To ask in terms of one-year survival the efficacy of haploidentical stem cell transplantation in children with refractory hematological malignancies. [ Time Frame: July 2006 ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: June 2003
Study Completion Date: February 2009
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Procedure: Stem Cell Transplantation
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Device: Miltenyi Biotec CliniMACS
stem cell selection device
Drug: Systemic chemotherapy and antibodies
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.
Other Names:
  • 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

Detailed Description:

Secondary objectives for this protocol are to 1) assess the kinetics of lymphohematopoietic reconstitution and 2) describe the short and long-term (up to 5 years post- transplant) toxicity of haploidentical stem cell transplantation, including GVHD, in children with refractory hematological malignancies.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Refractory hematological malignancies (chemoresistant relapse or primary induction failure) including:

  • 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
  • Patients with a performance score (Lansky/Karnofsky) of greater than or equal to 50
  • Must have a suitable family member donor that is HIV negative, greater than or equal to 18 years of age available for stem cell donation

Exclusion Criteria:

  • Patients with a known allergy to murine products
  • (Female Patients) Patient is pregnant
  • Female Patients) Patient is lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00145613

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Gregory Hale, M.D. St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Gregory Hale, M.D. / Principal Investigator, St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00145613     History of Changes
Other Study ID Numbers: REFSCT
Study First Received: September 1, 2005
Last Updated: February 12, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Haploidentical stem cell transplant
High risk hematologic malignancies
Allogeneic stem cell transplant
Mismatched family member stem cell donor

Additional relevant MeSH terms:
Hemoglobinuria
Hemoglobinuria, Paroxysmal
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Neoplasm Metastasis
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Anemia
Anemia, Hemolytic
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms by Histologic Type
Neoplastic Processes

ClinicalTrials.gov processed this record on October 23, 2014