Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

NCT00143559 | Completed Phase 2 DMC

• 1 other identifier: HAPREF
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including 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 body tissues of the patient (the host) 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 significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives. This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.

Conditions

Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Paroxysmal Nocturnal Hemoglobinuria; Hodgkin's Lymphoma; Non-Hodgkin Lymphoma

Keywords

Allogeneic stem cell transplantation; Haploidentical stem cell transplant; Mismatched family member stem cell donor transplant; Bone marrow transplant; High risk hematological malignancies; T-cell depletion methodology; Miltenyi Biotec CliniMACS stem cell selection device

Outcome Measures

Primary Outcomes (1)

• To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device.

  September 2006

Study Arms (1)

1

OTHER

Drug: Systematic chemotherapy and antibodies; Procedure: Allogeneic stem cell transplantation; Device: Miltenyi CliniMACS

Interventions

Systematic chemotherapy and antibodies DRUG

Systemic chemotherapy and antibodies as follows: Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD

1

Allogeneic 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 CliniMACS DEVICE

Miltenyi Biotec CliniMACS stem cell selection device

Also known as: Haploidentical donor stem cell transplant, Mismatched family member transplant, Allogeneic stem cell transplant, Reduced intensity conditioning regimen, Hematopoietic stem cell transplant

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:

• Eligible participants were assigned to one of two different strata dependent on diagnosis, disease status and/or past transplant experience. Both strata received the same intervention but will be followed and analyzed separately.
• Group A must have one of the following diagnosis
• Acute lymphoid leukemia (ALL) in second or subsequent remission or high risk in first remission
• Acute myeloid leukemia (AML) in remission or with ≤ 25% blasts in bone marrow
• Chronic myeloid leukemia (CML)
• Juvenile myelomonocytic leukemia (JMML)
• Myelodysplastic syndrome (MDS)
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) in second or subsequent remission after autologous HSCT, or unable to have hematopoietic stem cells collected for autologous HSCT
• Group B must have one of the following refractory diagnosis (chemoresistant relapse or primary induction failure)
• Acute lymphoid leukemia (ALL)
• Acute myeloid leukemia (AML) ≥ 25% blast in bone marrow
• Secondary AML / MDS
• Chronic myeloid leukemia (CML) in accelerated phase or blast crisis
• Juvenile myelomonocytic leukemia (JMML)

You may not qualify if:

• Known allergy to murine products
• Lactating (female patient)
• Pregnancy (female patient)
• Active central nervous system (CNS) leukemia

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

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

Interventions

Antibodies; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

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: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 2, 2005
• Study Start: August 1, 2005
• Primary Completion: July 1, 2006
• Study Completion: January 1, 2009
• Last Updated: January 29, 2009

Record last verified: 2009-01

Locations

US (1)