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

NCT01823198 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 2012-0819NCI-2013-00993RP110553-P3
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Erythroid Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blasts Under 20 Percent of Bone Marrow Nucleated Cells; Blasts Under 20 Percent of Peripheral Blood White Cells; Chronic Myelomonocytic Leukemia; High Risk Myelodysplastic Syndrome; Myelodysplastic Syndrome; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

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

  Participants that experienced DLT related to the NK Cells post transplant at different dose levels.

  Up to 42 days

Secondary Outcomes (2)

• Overall Survival

  Up to 2 years

• Number of Participants With Grade 3 Toxicities

  Up to day 42

Study Arms (1)

Treatment (NK cells, PBSC transplant)

EXPERIMENTAL

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.

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

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (NK cells, PBSC transplant)

Allogeneic CD56-positive CD3-negative Natural Killer Cells BIOLOGICAL

Given IV

Treatment (NK cells, PBSC transplant)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (NK cells, PBSC transplant)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (NK cells, PBSC transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (NK cells, PBSC transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (NK cells, PBSC transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (NK cells, PBSC transplant)

Pharmacological Study OTHER

Correlative studies

Treatment (NK cells, PBSC transplant)

Eligibility Criteria

• Age: 7 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Blast Crisis; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

aldesleukin; Busulfan; fludarabine phosphate; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Richard Champlin, MD / Stem Cell Transplantation Department
• Organization: University of Texas MD Anderson Cancer Center

rchampli@mdanderson.org

713-792-3618

Study Officials

• Richard E Champlin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 4, 2013
• Study Start: June 11, 2013
• Primary Completion: May 10, 2022
• Study Completion: May 10, 2022
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-11

Locations

US (1)