Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

• Status: Terminated
• Trial end date: 2016-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Mechlorethamine; Melphalan; Rituximab; Thiotepa; Vidarabine

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.