Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

St. Jude Children's Research Hospital

Status and phase

Terminated

Phase 2

Conditions

Myeloid Sarcoma

Acute Lymphoblastic Leukemia (ALL)

Non-Hodgkin Lymphoma (NHL)

Myelodysplastic Syndrome (MDS)

Acute Myeloid Leukemia (AML)

Juvenile Myelomonocytic Leukemia (JMML)

Chronic Myelogenous Leukemia (CML)

Treatments

Drug: Melphalan

Biological: Interleukin-2

Biological: G-CSF

Drug: Thiotepa

Drug: Fludarabine

Drug: Rituximab

Biological: T-cell depleted HPC transplant

Biological: CD45RA-depleted HPC transplant

Biological: Natural killer cell therapy

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT02259348

REFNK1

NCI-2014-01925 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

12 participants in 1 patient group

Participants

Experimental group

Description:

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.

Treatment: