T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant

NCT01621477 | Terminated Phase 2 Results

• 2 other identifiers: HAP3RNCI-2012-00554
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this protocol is to evaluate if the one-year survival is significantly improved in the group of patients who receive a T-cell replete haploidentical donor hematopoietic cell transplant (HCT) with a novel reduced intensity conditioning regimen. Study population will consist of patients (21 years or under) with hematologic malignancies that have relapsed or are refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft-versus-host disease (GvHD) at day 100. The investigators will describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment and study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

Conditions

Acute Lymphoblastic Leukemia; Acute Myelocytic Leukemia; Chronic Myelocytic Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Hodgkin or Non-Hodgkin Lymphoma; Sarcoma, Myeloid

Keywords

Hematologic malignancy; Hematopoietic cell transplant

Outcome Measures

Primary Outcomes (1)

• One-year Survival (OS)

  Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given.

  One year post transplant

Secondary Outcomes (6)

• Incidence of Malignant Relapse

  One year post transplantation.

• Event-Free Survival (EFS)

  one year post transplant

• Disease-Free Survival (DFS)

  one year post transplant

• Incidence and Severity of Acute Graft Versus Host Disease (GVHD)

  100 days post transplant

• Incidence and Severity of Chronic Graft Versus Host Disease (GVHD)

  100 days post transplant

Study Arms (1)

Treatment

EXPERIMENTAL

All study participants. Interventions: clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, mycophenolate mofetil

Drug: clofarabine; Drug: cytarabine; Drug: busulfan; Drug: Plerixafor; Drug: cyclophosphamide; Drug: antithymocyte globulin (rabbit); Biological: stem cells; Drug: Tacrolimus; Drug: mycophenolate mofetil

Interventions

clofarabine DRUG

Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent

Also known as: Cl-F-Ara-A, CAFdA, Clofarex, Clolar(TM)

Treatment

cytarabine DRUG

Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent

Also known as: Ara-C

Treatment

busulfan DRUG

Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent

Also known as: Myleran(R), Busulfex

Treatment

Plerixafor DRUG

Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer

Also known as: AMD3100, Mozobil(R)

Treatment

cyclophosphamide DRUG

Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.

Also known as: Cytoxan

Treatment

antithymocyte globulin (rabbit) DRUG

Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

Also known as: Rabbit ATG, Rabbit Thymoglobulin(R)

Treatment

stem cells BIOLOGICAL

Patients undergo T cell replete Hematopoietic stem cell infusion on Day 0 and Day +1. Patients undergo natural killer (NK) cell transplantation on day +6 (Day 0 is first stem cell infusion).

Also known as: HSC infusion

Treatment

Tacrolimus DRUG

Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

Also known as: FK506, Prograf(R), Protonic(R)

Treatment

mycophenolate mofetil DRUG

Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

Also known as: MMF, CellCept(R)

Treatment

Eligibility Criteria

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

You may qualify if:

• Age less than 21 years.
• One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT:
• Acute lymphoblastic leukemia (ALL)
• Acute myeloid leukemia (AML) (including myeloid sarcoma)
• Chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), Hodgkin or non-Hodgkin lymphoma (NHL)
• Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
• Does not have any other active malignancy other than the one for which this transplant is indicated.
• If prior central nervous system (CNS) leukemia, it must be treated and have no evidence of CNS disease
• Does not have current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator.
• Patient must fulfill pre-transplant evaluation:
• Left ventricular ejection fraction greater than 40%, or shortening fraction greater than or equal to 25%.
• Creatinine clearance or Glomerular Filtration Rate of ≥70 ml/min/1.73m\^2.
• Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing.
• Karnofsky or Lansky (age-dependent) performance score ≥ 50.
• Total bilirubin ≤ 1.5 times the upper limit of normal for age.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Assisi Foundation: collaborator

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

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Sarcoma, Myeloid; Hematologic Neoplasms

Interventions

Clofarabine; Cytarabine; Busulfan; plerixafor; Cyclophosphamide; thymoglobulin; Tacrolimus; Mycophenolic Acid

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; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Lymphoma; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

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

brandon.triplett@stjude.org

901-595-2766

Study Officials

• Brandon M. 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: June 8, 2012
• First Posted: June 18, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 20, 2017
• Results First Posted: February 20, 2017

Record last verified: 2016-12

Locations

US (1)