NCT01823198 · REGISTRY CONDITION SEARCH

Donor Natural Killer Cells and Donor Stem Cell Transplant in Treating Patients With High Risk Myeloid Malignancies

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2023-11-07

This phase I/II trial studies the side effects and best dose of donor natural killer cells when given together with donor stem cell transplant and to see how well they work in treating patients with myeloid malignancies that are likely to come back or spread. Giving chemotherapy, such as busulfan and fludarabine phosphate, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants Who Experienced Dose-limiting Toxicities (DLT)

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outcome · POSTED

Overall Survival

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outcome · POSTED

Number of Participants With Grade 3 Toxicities

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Acute myeloid leukemia who fail to achieve complete remission with one course of induction chemotherapy or after relapse; patients must have less than 20% bone marrow or peripheral blood blasts * Acute myeloid leukemia in first remission with any of the following high risk features defined as: * Adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (\> 3 abnormalities) * Preceding myelodysplastic or myeloproliferative syndrome * Presence of high risk molecular abnormalities including FLT3 mutations, DNMT3A, TET2; ras; kit * French-American-British (FAB) monosomy (M)6 or M7 classification * Treatment related acute myeloid leukemia (AML) * Residual cytogenetic or molecular abnormalities * Myelodysplastic syndromes with intermediate, high or very high risk Revised International Prognostic Scoring System (R-IPSS) score, chronic myelomonocytic leukemia (CMML) or therapy related myelodysplastic syndromes (MDS) * Chronic myeloid leukemia (CML) which: * Failed to achieve a cytogenetic remission to tyrosine kinase inhibitor treatment or has a cytogenetic relapse * Has ever been in accelerated phase or blast crisis * Patient must have an identified HLA (A,B,C,DR) compatible related or unrelated donor who is age 16 years of age or older and weighs at least 110 pounds for the stem cell donation * Zubrod performance status 0 to 2 or Karnofsky of at least 60 * Left ventricular ejection fraction \>= 45%; no uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease * Forced expiratory volume in one second (FEV1) \>= 50% of expected, corrected for hemoglobin * Forced vital capacity (FVC) \>= 50% of expected, corrected for hemoglobin * Diffusing capacity of the lung for carbon monoxide (DLCO) \>= 50% of expected, corrected for hemoglobin * Bilirubin =\< 1.5 mg/dl (unless Gilbert's syndrome) * Serum glutamate pyruvate transaminase (SGPT) =\< 200 IU/ml unless related to patient malignancy * Hepatitis B surface antigen negative and hepatitis C antibody negative * No evidence of chronic active hepatitis or cirrhosis * Patients with a history of hepatitis C, but have a negative viral load, are eligible * The protocol chairman will determine the eligibility of patients related to hepatic abnormalities * Serum creatinine \< 1.5 mg% * Patient or patient's legal representative, parent(s) or guardian able to sign informed consent; patients aged 7 to \< 18 to provide assent * Pediatric patients (age 7-18 years) will be entered only after 3 adult patients have been entered without dose limiting toxicity Exclusion Criteria: * Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy; the protocol principal investigator (PI) is the final arbiter of eligibility * Pleural/pericardial effusion or ascites \> 1 L * Patients who are known to be human immunodeficiency virus (HIV)-seropositive * Pregnancy: positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization * Women of child bearing potential not willing to use an effective contraceptive measure while on study * Patients who are known to have allergy to mouse proteins
healthy Volunteers: false
maximum Age: 65 Years
minimum Age: 7 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive fludarabine phosphate IV over 1 hour and busulfan IV over 3 hours on days -13 to -10. Patients then receive allogeneic CD56-positive CD3-negative natural killer cells IV over 1 hour on day -8. Patients also receive aldesleukin SC QD on days -8 to -4. Patients then undergo allogeneic PBSC transplant on day 0.
intervention Names
Biological: Aldesleukin
Biological: Allogeneic CD56-positive CD3-negative Natural Killer Cells
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Busulfan
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Procedure: Peripheral Blood Stem Cell Transplantation
Other: Pharmacological Study
label
Treatment (NK cells, PBSC transplant)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Given SC
name
Aldesleukin
other Names
125-L-Serine-2-133-interleukin 2
Proleukin
r-serHuIL-2
Recombinant Human IL-2
Recombinant Human Interleukin-2
type
BIOLOGICAL
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Given IV
name
Allogeneic CD56-positive CD3-negative Natural Killer Cells
type
BIOLOGICAL
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Undergo allogeneic PBSC transplant
name
Allogeneic Hematopoietic Stem Cell Transplantation
other Names
Allogeneic Hematopoietic Cell Transplantation
Allogeneic Stem Cell Transplantation
HSC
HSCT
type
PROCEDURE
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Given IV
name
Busulfan
other Names
1, 4-Bis[methanesulfonoxy]butane
BUS
Bussulfam
Busulfanum
Busulfex
Busulphan
CB 2041
CB-2041
Glyzophrol
GT 41
GT-41
Joacamine
type
DRUG
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Given IV
name
Fludarabine Phosphate
other Names
2-F-ara-AMP
9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
Beneflur
Fludara
SH T 586
type
DRUG
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Undergo allogeneic PBSC transplant
name
Peripheral Blood Stem Cell Transplantation
other Names
PBPC transplantation
PBSCT
Peripheral Blood Progenitor Cell Transplantation
Peripheral Stem Cell Support
Peripheral Stem Cell Transplant
Peripheral Stem Cell Transplantation
type
PROCEDURE
arm Group Labels
Treatment (NK cells, PBSC transplant)
description
Correlative studies
name
Pharmacological Study
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 63
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Participants that experienced DLT related to the NK Cells post transplant at different dose levels.
measure
Number of Participants Who Experienced Dose-limiting Toxicities (DLT)
time Frame
Up to 42 days

secondary Outcomes

description
Participants that survived between day of transplant and day of death on different dose levels.
measure
Overall Survival
time Frame
Up to 2 years
description
Number of participants that had grade 3 toxicities up to day 42.
measure
Number of Participants With Grade 3 Toxicities
time Frame
Up to day 42

Full study description

brief Summary: This phase I/II trial studies the side effects and best dose of donor natural killer cells when given together with donor stem cell transplant and to see how well they work in treating patients with myeloid malignancies that are likely to come back or spread. Giving chemotherapy, such as busulfan and fludarabine phosphate, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
detailed Description: PRIMARY OBJECTIVES: I. Assess the safety of infusing ex vivo expanded natural killer (NK) cells in patients receiving busulfan-fludarabine phosphate (fludarabine) with an allogeneic human leukocyte antigen (HLA) matched hematopoietic transplantation for myeloid malignancies. Two sources of NK cells could be studied, depending on what donor source is available: cells from the HLA matched related donor or cells from an unrelated cord blood unit. II. For each source of NK cells: the maximum tolerated cell dose; the phenotype and function of the ex vivo expanded NK cells and their survival in vivo; the rate of engraftment, graft-vs.-host disease (GVHD), immune reconstitution, relapse rates and survival for patients receiving this regimen will be determined. OUTLINE: This is a phase I, dose-escalation study of NK cells followed by a phase II study. Patients receive fludarabine phosphate intravenously (IV) over 1 hour and busulfan IV over 3 hours on days -13 to -10. Patients then receive allogeneic CD56-positive CD3-negative natural killer cells IV over 1 hour on day -8. Patients also receive aldesleukin subcutaneously (SC) once daily (QD) on days -8 to -4. Patients then undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

Source references