Natural Killer Cells Before and After Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia

NCT01904136 | Completed Phase 1 Results FDA Drug

• 6 other identifiers: 2012-0708NCI-2013-02183P01 - 5P01RP110553 05-07-0483205-07-04832P01CA049639
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II studies the side effects and best dose of natural killer cells before and after donor stem cell transplant and to see how well they work in treating patients with acute myeloid leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia. Giving chemotherapy with or without total body irradiation before a donor peripheral blood stem cell or bone marrow 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 Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Gene Mutations; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  Number of participants that experienced dose limiting toxicities.

  Up to day 70 post-transplant

Secondary Outcomes (2)

• 100-day Treatment Related Mortality

  Up to 100 days post-transplant

• Overall Survival

  Up to 2 years

Study Arms (1)

Treatment (NK cells, allogeneic stem cell transplant)

EXPERIMENTAL

MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1. NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1. TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0. POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months. NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Bone Marrow Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Mycophenolate Mofetil; Biological: Natural Killer Cell Therapy; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

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

Treatment (NK cells, allogeneic stem cell transplant)

Bone Marrow Transplantation PROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

Also known as: Blood and Bone Marrow Transplant, BMT, Bone Marrow Grafting, Bone Marrow Transplant, Marrow Transplantation

Treatment (NK cells, allogeneic stem cell transplant)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (NK cells, allogeneic stem cell transplant)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (NK cells, allogeneic stem cell transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (NK cells, allogeneic stem cell transplant)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (NK cells, allogeneic stem cell transplant)

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

Treatment (NK cells, allogeneic stem cell transplant)

Natural Killer Cell Therapy BIOLOGICAL

Given IV

Treatment (NK cells, allogeneic stem cell transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC or bone marrow 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, allogeneic stem cell transplant)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (NK cells, allogeneic stem cell transplant)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Treatment (NK cells, allogeneic stem cell transplant)

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age 2-17 years old may be enrolled after at least 4 adults (ages 18-65 years old) have been treated without toxicity
• Patient with no matched related donor who has a related haploidentical donor identified (=\< 7/8 allele match at the A, B, C, DR loci) who is willing to undergo a bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's admission for transplant; the donor must be 16 years of age or older and weigh at least 110 pounds
• Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as: (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g. DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (\> 3 abnormalities); (vi) treatment-related AML, or b. second or greater remission; patients beyond second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
• Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy, or b. patients with treatment-related MDS
• Chronic myeloid leukemia (CML): a. failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b. accelerated phase or blast phase at any time
• Performance score of at least 70% by Karnofsky or 0 to 1 by Eastern Cooperative Oncology Group (ECOG) (age \>= 12 years), or Lansky Play-performance scale of at least 70% or greater (age \< 12 years)
• Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-Gault formula)
• Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or less than 200 IU/ml for adults
• Conjugated (direct) bilirubin less than 2 x upper limit of normal
• Left ventricular ejection fraction equal or greater than 40%
• Diffusing capacity of the lung for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin; for children =\< 7 years of age who are unable to perform pulmonary function tests (PFT), oxygen saturation \>= 92% on room air by pulse oximetry
• Patient or patient's legal representative, parent(s) or guardian should provide written informed consent; assent of a minor if participant's age is at least seven and less than eighteen years

You may not qualify if:

• Human immunodeficiency virus (HIV) positive; active hepatitis B or C
• Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion
• Liver cirrhosis
• Central nervous system (CNS) involvement within 3 months
• Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
• Inability to comply with medical therapy or follow-up

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 Publications (1)

• Ciurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, Olson A, Bashir Q, Gulbis AM, Indreshpal K, Rezvani K, Shpall EJ, Bassett R, Cao K, Martin AS, Devine S, Horowitz M, Pasquini M, Lee DA, Champlin RE. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022 Jan;36(1):155-164. doi: 10.1038/s41375-021-01349-4. Epub 2021 Jul 26.

  PMID: 34312462 DERIVED

MeSH Terms

Conditions

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

Interventions

Stem Cell Transplantation; Bone Marrow Transplantation; Blood Specimen Collection; Cyclophosphamide; fludarabine; Melphalan; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Whole-Body Irradiation

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Macrolides; Lactones; Radiotherapy

Results Point of Contact

• Title: UT MD Anderson Cancer Center
• Organization: Samer Srour, MD / Stem Cellular Transplantation Department

ssrour@mdanderson.org

713-794-4354

Study Officials

• Samer Srour

  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: July 17, 2013
• First Posted: July 22, 2013
• Study Start: April 22, 2014
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: January 24, 2024
• Results First Posted: January 17, 2024

Record last verified: 2024-01

Locations

US (1)