Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies

NCT00566696 | Completed Phase 2 Results DMC

• 2 other identifiers: HIFLEXNCI-2011-03670
• Study Type: interventional
• Target: 73
• 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 (HAPLO) 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. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.

Conditions

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

Keywords

Haploidentical stem cell transplant; Allogeneic stem cell transplant; Mismatched family member stem cell donor transplant; Bone marrow transplant; High risk hematologic malignancies; T cell depletion methodology; Miltenyi Biotec CliniMACS stem cell selection device; Campath-1H intravenous

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS)

  To determine if one year event-free survival can be improved in pediatric patients undergoing a haploidentical transplant by using a reduced intensity conditioning regimen and a targeted dose T cell depleted donor product. EFS is defined as time from transplantation to the occurrence of relapse or death due to any cause. Patients who are alive at the time of analysis will be censored. The estimated percentage of participants with EFS at one-year post-transplantation is reported using Kaplan-Meier analysis.

  one year post-transplant

Secondary Outcomes (6)

• Overall Survival (OS)

  one year post-transplant

• Disease-Free Survival (DFS)

  One year post-transplant

• Incidence of Non-hematologic Regimen-related Toxicities

  100 days post-transplant

• Incidence of Regimen-related Mortality

  100 days post-transplant

• To Estimate the Cumulative Incidence of Relapse for Research Participants Who Receive This Study Treatment.

  five years post-transplant

Study Arms (1)

High-Risk Hematologic Malignancies

EXPERIMENTAL

Participants meeting eligibility criteria undergo haploidentical stem cell transplantation along with systemic chemotherapy and antibodies, including Fludarabine, Thioplex®, L-phenylalanine mustard, mycophenolate mofetil, CellCept®, Rituxan™, Muromonab (prior to January 2010) or Alemtuzumab (after January 2010), Cyclophosphamide, Anti-thymocyte globulin (Rabbit), and G-CSF. Grafts from suitable haploidentical donors are processed using the CliniMACS system.

Device: CliniMACS; Procedure: Stem cell transplantation; Drug: Fludarabine; Drug: Thioplex®; Drug: L-phenylalanine mustard; Drug: Mycophenolate mofetil; Drug: Rituxan™; Drug: Alemtuzumab; Drug: Cyclophosphamide; Drug: Anti-thymocyte globulin (Rabbit); Drug: G-CSF; Drug: Muromonab

Interventions

CliniMACS DEVICE

Miltenyi Biotec CliniMACS stem cell selection device

High-Risk Hematologic Malignancies

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.

High-Risk Hematologic Malignancies

Fludarabine DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Fludara

High-Risk Hematologic Malignancies

Thioplex® DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Thiotepa, TESPA, TSPA

High-Risk Hematologic Malignancies

L-phenylalanine mustard DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Melphalan, Phenylalanine mustard, L-PAM, L-sarcolysin, Alkeran

High-Risk Hematologic Malignancies

Mycophenolate mofetil DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: MMF, CellCept®

High-Risk Hematologic Malignancies

Rituxan™ DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Rituximab

High-Risk Hematologic Malignancies

Alemtuzumab DRUG

After January 2010, due to the unavailability of muromonab, transplant recipients received a conditioning regimen consisting of systemic chemotherapy and antibodies, including alemtuzumab.

Also known as: Campath-1H, Campath®

High-Risk Hematologic Malignancies

Cyclophosphamide DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Cytoxan

High-Risk Hematologic Malignancies

Anti-thymocyte globulin (Rabbit) DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Thymoglobulin®, Rabbit ATG

High-Risk Hematologic Malignancies

G-CSF DRUG

Transplant recipients will receive a conditioning regimen consisting of systemic chemotherapy and antibodies.

Also known as: Filgrastim, Neupogen®

High-Risk Hematologic Malignancies

Muromonab DRUG

Prior to January 2010, transplant participants received a conditioning regimen consisting of systemic chemotherapy and antibodies, including muromonab. Muromonab became unavailable from the manufacturer at that time and was replaced by alemtuzumab.

Also known as: OKT3, Muromonab-CD3

High-Risk Hematologic Malignancies

Eligibility Criteria

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

You may qualify if:

• Patients less than or equal to 21 years of age; may be greater than 21 years old if a current St. Jude patient or previously treated St. Jude patient within 3 years of completion of prior treatment.
• Must have one of the following diagnosis:
• ALL high risk in second remission. Examples include relapse on therapy, first remission duration of less than or equal to 30 months, or relapse within 12 months of completing therapy.
• ALL in third or subsequent remission.
• ALL high risk in first remission. Examples include: induction failure, minimal residual disease greater than or equal to 1% marrow blasts by morphology after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission.
• High-risk AML in first remission. Examples include monosomy 7, M6, M7, t(6;9), FLT3-ITD, or patients who have greater than or equal to 25% blasts by morphology after induction or who do not achieve CR after 2 courses of therapy (includes myeloid sarcoma).
• Relapsed or persistent AML (less than or equal to 25% blasts in marrow by morphology).
• AML in second or subsequent morphologic remission (includes myeloid sarcoma).
• CML in first chronic phase with detectable molecular or cytogenetic evidence of disease despite medical therapy; or CML with a history of accelerated or blast crisis, now in chronic phase; or unable to tolerate tyrosine kinase inhibitor therapy.
• Juvenile myelomonocytic leukemia (JMML).
• Myelodysplastic syndrome (MDS).
• Therapy related (secondary) AML, ALL, or MDS.
• Hodgkin lymphoma after failure of prior autologous HSCT or unsuitable for autologous HSCT.
• Non-Hodgkin lymphoma (NHL) in second complete remission (CR2) or subsequent.
• Has not received a prior allogeneic hematopoietic stem cell transplant.

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
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Juvenile; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Hodgkin Disease; Lymphoma; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes

Interventions

Stem Cell Transplantation; fludarabine; fludarabine phosphate; Thiotepa; Melphalan; Mycophenolic Acid; Rituximab; Alemtuzumab; Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Granulocyte Colony-Stimulating Factor; Filgrastim; Muromonab-CD3

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anemia, Hemolytic; Anemia; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Phosphoramide Mustards; Immune Sera; Biological Products; Complex Mixtures; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Immunoglobulin G; Immunoglobulin Isotypes

Results Point of Contact

• Title: Brandon Triplett, MD
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

866-278-5833

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2007
• First Posted: December 3, 2007
• Study Start: December 14, 2007
• Primary Completion: January 27, 2016
• Study Completion: February 6, 2020
• Last Updated: April 14, 2020
• Results First Posted: May 3, 2016

Record last verified: 2019-10

Locations

US (1)