Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

NCT02259348 | Terminated Phase 2 Results

• 2 other identifiers: REFNK1NCI-2014-01925
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.

Conditions

Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myelogenous Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

Keywords

Hematological malignancies; Allogeneic hematopoietic cell transplant; Refractory hematologic malignancy; Relapsed hematologic malignancy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Engrafted by Day 42 Post-transplant

  To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm\^3 with evidence of donor cell engraftment.

  Day 42 post transplantation

Secondary Outcomes (6)

• Incidence of Malignant Relapse

  one year post transplantation

• Event-free Survival (EFS)

  one year post transplantation

• Overall Survival (OS)

  one year post transplantation

• Incidence and Severity of Acute GvHD

  100 days post transplantation

• Incidence and Severity of Chronic GvHD

  one year post transplantation

Study Arms (1)

Participants

EXPERIMENTAL

Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: G-CSF; Biological: Interleukin-2; Drug: Melphalan; Drug: Thiotepa; Drug: Rituximab; Biological: Natural killer cell therapy; Biological: T-cell depleted HPC transplant; Biological: CD45RA-depleted HPC transplant

Interventions

Cyclophosphamide DRUG

Given intravenously (IV)

Also known as: Cytoxan

Participants

Fludarabine DRUG

Given IV

Also known as: Fludara, Fludarabine monophosphate

Participants

G-CSF BIOLOGICAL

Given IV or subcutaneously (SQ)

Also known as: Filgrastim, Neupogen®

Participants

Interleukin-2 BIOLOGICAL

Given SQ

Also known as: IL-2, Aldesleukin

Participants

Melphalan DRUG

Given IV

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

Participants

Thiotepa DRUG

Given IV

Also known as: ThioplexV, TESPA, TSPA

Participants

Rituximab DRUG

Given IV

Also known as: Rituxan™

Participants

Natural killer cell therapy BIOLOGICAL

Given IV

Also known as: NK cell therapy

Participants

T-cell depleted HPC transplant BIOLOGICAL

T-cell depleted hematopoietic stem cells will be infused on day 0.

Also known as: HPC,A Infusion(ɑ/β T cell depleted)

Participants

CD45RA-depleted HPC transplant BIOLOGICAL

CD45RA depleted stem cells will be infused on day 1.

Participants

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 or equal to 21 years.
• One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplant (HCT):
• ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), 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 in CNS complete remission (CR)
• Does not have current uncontrolled bacterial, fungal, or viral infection.
• Patient must fulfill pre-transplant evaluation:
• Left ventricular ejection fraction \> 40%, or shortening fraction ≥ 25%.
• Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.
• 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 (See Appendix A).
• Bilirubin ≤ 3 times the upper limit of normal for age.
• Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.
• Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.

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

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

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Granulocyte Colony-Stimulating Factor; Filgrastim; Interleukin-2; aldesleukin; Melphalan; Thiotepa; Rituximab

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Lymphokines; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Limitations and Caveats

The trial was terminated early due to investigator's decision.

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 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: October 3, 2014
• First Posted: October 8, 2014
• Study Start: October 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: March 1, 2016
• Last Updated: May 30, 2017
• Results First Posted: May 2, 2016

Record last verified: 2016-09

Locations

US (1)