Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

NCT ID: NCT02259348

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2016-03-31

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.

Detailed Description

PRIMARY OBJECTIVE:

• 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 natural killer (NK) cells.

SECONDARY OBJECTIVES:

• Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
• Estimate incidence and severity of acute and chronic (GvHD).
• Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins.

Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell transplantation that includes chemotherapy medications and natural killer cells in preparation for transplantation. They will then receive T-cell depleted HPC transplant followed by CD45RA-depleted HPC transplant the following day.

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants

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.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given intravenously (IV)

Fludarabine

Intervention Type: DRUG

Given IV

G-CSF

Intervention Type: BIOLOGICAL

Given IV or subcutaneously (SQ)

Interleukin-2

Intervention Type: BIOLOGICAL

Given SQ

Melphalan

Intervention Type: DRUG

Given IV

Thiotepa

Intervention Type: DRUG

Given IV

Rituximab

Intervention Type: DRUG

Given IV

Natural killer cell therapy

Intervention Type: BIOLOGICAL

Given IV

T-cell depleted HPC transplant

Intervention Type: BIOLOGICAL

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

CD45RA-depleted HPC transplant

Intervention Type: BIOLOGICAL

CD45RA depleted stem cells will be infused on day 1.

Interventions

Cyclophosphamide

Given intravenously (IV)

Intervention Type: DRUG

Fludarabine

Given IV

Intervention Type: DRUG

G-CSF

Given IV or subcutaneously (SQ)

Intervention Type: BIOLOGICAL

Interleukin-2

Given SQ

Intervention Type: BIOLOGICAL

Melphalan

Given IV

Intervention Type: DRUG

Thiotepa

Given IV

Intervention Type: DRUG

Rituximab

Given IV

Intervention Type: DRUG

Natural killer cell therapy

Given IV

Intervention Type: BIOLOGICAL

T-cell depleted HPC transplant

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

Intervention Type: BIOLOGICAL

CD45RA-depleted HPC transplant

CD45RA depleted stem cells will be infused on day 1.

Intervention Type: BIOLOGICAL

Other Intervention Names

Cytoxan; Fludara; Fludarabine monophosphate; Filgrastim; Neupogen®; IL-2; Aldesleukin; L-phenylalanine mustard; Phenylalanine mustard; L-PAM; L-sarcolysin; Alkeran®; ThioplexV; TESPA; TSPA; Rituxan™; NK cell therapy; HPC,A Infusion(ɑ/β T cell depleted)

Eligibility Criteria

Inclusion Criteria

• 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.
• Not breast feeding
• DONOR: At least single haplotype matched (≥ 3 of 6) family member
• DONOR: At least 18 years of age.
• DONOR: HIV negative.
• DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
• DONOR: Not breast feeding.
• DONOR: Regarding donation eligibility, is identified as either:

• Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
• Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.

• 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

Responsibility Role: SPONSOR

Principal Investigators

Brandon Triplett, MD

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

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2014-01925

Identifier Type: REGISTRY

Identifier Source: secondary_id

REFNK1

Identifier Type: -

Identifier Source: org_study_id