Myelodysplastic Syndrome Clinical Trial

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

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.

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Full 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.

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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

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 1

Estimated Enrollment:

63

Study ID:

NCT01823198

Recruitment Status:

Completed

Sponsor:

M.D. Anderson Cancer Center

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Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 1

Estimated Enrollment:

63

Study ID:

NCT01823198

Recruitment Status:

Completed

Sponsor:


M.D. Anderson Cancer Center

How clear is this clinincal trial information?

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