Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

NCT ID: NCT00143559

Last Updated: 2009-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-01-31

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.

Detailed Description

Secondary outcome evaluations for this clinical study included the following:

• To estimate one-year overall survival for research participants with high risk malignancies who receive a haploidentical HSCT
• To compare overall survival and cumulative incidence of relapse for the two groups of patients with their corresponding historical controls
• To estimate disease-free survival and event-free survival in participants with hematologic malignancies who receive a haploidentical HSCT
• To estimate the incidence of overall grade 3-4 acute GvHD in research participants with hematologic malignancies who receive a haploidentical HSCT
• To estimate the incidence of chronic GvHD and graft failure in research participants with hematologic malignancies who receive a haploidentical HSCT
• To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant in research participants with hematologic malignancies who receive a haploidentical HSCT
• To estimate the number of research participants who develop evidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
• To describe disease-free survival, GvHD and engraftment in research participants receiving grafts from Killer immunoglobulin-like receptor (KIR) mismatched and KIR matched haploidentical donors

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: OTHER

Systematic chemotherapy and antibodies

Intervention Type: 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

Allogeneic stem cell transplantation

Intervention Type: PROCEDURE

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

Miltenyi CliniMACS

Intervention Type: DEVICE

Miltenyi Biotec CliniMACS stem cell selection device

Interventions

Systematic chemotherapy and antibodies

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

Intervention Type: DRUG

Allogeneic stem cell transplantation

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

Intervention Type: PROCEDURE

Miltenyi CliniMACS

Miltenyi Biotec CliniMACS stem cell selection device

Intervention Type: DEVICE

Other Intervention Names

Haploidentical donor stem cell transplant; Mismatched family member transplant; Allogeneic stem cell transplant; Reduced intensity conditioning regimen; Hematopoietic stem cell transplant

Eligibility Criteria

Inclusion Criteria

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)
• Myelodysplastic syndrome (MDS)
• Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) with residual disease followed by autologous HSCT or who have chemo-resistant disease
• Or patients who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of the Transplant Faculty makes standard myeloablation prohibited
• At least 2 and less than or equal to 21 years of age
• Lacks suitable HLA-identical sibling or matched available unrelated donor and has a mismatched family member donor that is available, HIV negative and at least 18 years old
• Cardiac shortening fraction ≥ 25%
• Creatinine clearance ≥ 40 cc/min/1.73m^2
• FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air
• Direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L
• Karnofsky or Lansky (age dependent) performance score of ≥ 50

Exclusion Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

St. Jude Children's Research Hospital

Principal Investigators

Gregory Hale, M.D.

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

Other Identifiers

HAPREF

Identifier Type: -

Identifier Source: org_study_id