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NCT01823198

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

Completed Phase 1, PHASE2 Results posted Last updated 7 November 2023
What this trial tests

Phase 1, PHASE2 trial testing Aldesleukin in Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive in 63 participants. Completed in 10 May 2022.

Timeline
11 June 2013
Primary endpoint
10 May 2022
10 May 2022

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment63
Start date11 June 2013
Primary completion10 May 2022
Estimated completion10 May 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

Adults 7 to 65, any sex, with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive or Acute Erythroid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced Dose-limiting Toxicities (DLT) Primary · Up to 42 days

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

Group A: NK cells from KIR mismatched haplo donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^71
Phase I: NK Cell Dose Level 3_ 3x10^70
Phase I: NK Cell Dose Level 4_ 10^80
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^80
Group B: NK cells from KIR mismatched cord blood donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^72
Phase I: NK Cell Dose Level 3_ 3x10^72
Phase I: NK Cell Dose Level 4_ 10^82
Phase II: NK Cell Dose Level 3_3x10^71
Phase II: NK Cell Dose Level 4_ 10^812
Group C: NK cells from matched related donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^73
Phase I: NK Cell Dose Level 3_ 3x10^72
Phase I: NK Cell Dose Level 4_ 10^82
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^89
Overall Survival Secondary · Up to 2 years

Participants that survived between day of transplant and day of death on different dose levels.

Group A: NK cells from KIR mismatched haplo donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^70
Phase I: NK Cell Dose Level 3_ 3x10^70
Phase I: NK Cell Dose Level 4_ 10^80
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^80
Group B: NK cells from KIR mismatched cord blood donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^61
Phase I: NK Cell Dose Level 2_10^71
Phase I: NK Cell Dose Level 3_ 3x10^70
Phase I: NK Cell Dose Level 4_ 10^81
Phase II: NK Cell Dose Level 3_3x10^71
Phase II: NK Cell Dose Level 4_ 10^87
Group C: NK cells from matched related donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^70
Phase I: NK Cell Dose Level 3_ 3x10^73
Phase I: NK Cell Dose Level 4_ 10^82
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^82
Number of Participants With Grade 3 Toxicities Secondary · Up to day 42

Number of participants that had grade 3 toxicities up to day 42.

Group A: NK cells from KIR mismatched haplo donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^71
Phase I: NK Cell Dose Level 3_ 3x10^70
Phase I: NK Cell Dose Level 4_ 10^80
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^80
Group B: NK cells from KIR mismatched cord blood donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^61
Phase I: NK Cell Dose Level 2_10^72
Phase I: NK Cell Dose Level 3_ 3x10^71
Phase I: NK Cell Dose Level 4_ 10^81
Phase II: NK Cell Dose Level 3_3x10^71
Phase II: NK Cell Dose Level 4_ 10^811
Group C: NK cells from matched related donors
GroupValue95% CI
Phase I: NK Cell Dose Level 1_10^62
Phase I: NK Cell Dose Level 2_10^72
Phase I: NK Cell Dose Level 3_ 3x10^72
Phase I: NK Cell Dose Level 4_ 10^82
Phase II: NK Cell Dose Level 3_3x10^70
Phase II: NK Cell Dose Level 4_ 10^86

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 42 days. All-Cause Mortality was monitored/assessed for up to 2 years).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I: NK Cell Dose Level 1_10^6
Serious: 1/6 (17%)
Deaths: 1/6
Phase I: NK Cell Dose Level 2_10^7
Serious: 2/6 (33%)
Deaths: 4/6
Phase I: NK Cell Dose Level 3_ 3x10^7
Serious: 1/4 (25%)
Deaths: 2/4
Phase I: NK Cell Dose Level 4_ 10^8
Serious: 0/4 (0%)
Deaths: 1/4
Phase II: NK Cell Dose Level 3_3x10^7
Serious: 1/1 (100%)
Deaths: 0/1
Phase II: NK Cell Dose Level 4_ 10^8
Serious: 6/21 (29%)
Deaths: 9/21
Donors
Serious: 0
Deaths: 0

Serious adverse events (9 terms)

ReactionSystemPhase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase II: NK Cell Dose Lev…Phase II: NK Cell Dose Lev…Donors
Liver GvHDHepatobiliary disorders———————
Viral InfectionsInfections and infestations———————
Chronic lung GvHDRespiratory, thoracic and mediastinal disorders———————
Secondary graft failureBlood and lymphatic system disorders———————
Fungal InfectionsInfections and infestations———————
Liver GvHDHepatobiliary disorders———————
GI GvHDGastrointestinal disorders———————
Chronic Skin GvHDSkin and subcutaneous tissue disorders———————
Bacterial InfectionsInfections and infestations———————
Other adverse events (34 terms — click to expand)

ReactionSystemPhase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase I: NK Cell Dose Leve…Phase II: NK Cell Dose Lev…Phase II: NK Cell Dose Lev…Donors
MucositisGastrointestinal disorders———————
NauseaGastrointestinal disorders———————
DiarrheaGastrointestinal disorders———————
Skin GvHDSkin and subcutaneous tissue disorders———————
Fluid overloadGeneral disorders———————
Elevated bilirubinInvestigations———————
Bacterial InfectionsInfections and infestations———————
Chronic ocular GvHDEye disorders———————
Neutropenic feversBlood and lymphatic system disorders———————
Viral InfectionsInfections and infestations———————
Chronic oral GvHDGastrointestinal disorders———————
Elevated transminitisInvestigations———————
BK virus associated hemorrhagic cystitisInfections and infestations———————
GI GvHDGastrointestinal disorders———————
RashSkin and subcutaneous tissue disorders———————
FeversGeneral disorders———————
Upper GI GvHDGastrointestinal disorders———————
DizzinessNervous system disorders———————
HeadacheNervous system disorders———————
HypertensionVascular disorders———————
PneumonitisRespiratory, thoracic and mediastinal disorders———————
Chronic Skin GvHDSkin and subcutaneous tissue disorders———————
Creatinine increasedInvestigations———————
Liver GvHDGastrointestinal disorders———————
ABO incompatibilityInvestigations———————
Allergic reactionImmune system disorders———————
Bronchiolitis obliterans with organizing pneumoniaRespiratory, thoracic and mediastinal disorders———————
Chronic Liver GvHDInvestigations———————
Chronic vaginal GvHDReproductive system and breast disorders———————
Ejection fraction decreasedCardiac disorders———————
Flu like syndromeGeneral disorders———————
Fungal InfectionsInfections and infestations———————
Idiopathic thrombocytopenic purpura (ITP)Investigations———————
Pleural EffusionRespiratory, thoracic and mediastinal disorders———————

Most-reported serious reactions: Liver GvHD, Viral Infections, Chronic lung GvHD, Secondary graft failure, Fungal Infections, Liver GvHD, GI GvHD, Chronic Skin GvHD.

Data from ClinicalTrials.gov NCT01823198 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Natural killer cells in clinical development as non-engineered, engineered, and combination therapies.
    Lamers-Kok N, Panella D, Georgoudaki AM, Liu H, et al · · 2022 · cited 125× · PMID 36348457 · DOI 10.1186/s13045-022-01382-5
  2. Human cell-based artificial antigen-presenting cells for cancer immunotherapy.
    Butler MO, Hirano N. · · 2014 · cited 99× · PMID 24329798 · DOI 10.1111/imr.12129
  3. Natural killer cell-based immunotherapy for acute myeloid leukemia.
    Xu J, Niu T. · · 2020 · cited 83× · PMID 33287858 · DOI 10.1186/s13045-020-00996-x
  4. Cord Blood as a Source of Natural Killer Cells.
    Mehta RS, Shpall EJ, Rezvani K. · · 2015 · cited 63× · PMID 26779484 · DOI 10.3389/fmed.2015.00093
  5. Anti-CD105 Antibody Eliminates Tumor Microenvironment Cells and Enhances Anti-GD2 Antibody Immunotherapy of Neuroblastoma with Activated Natural Killer Cells.
    Wu HW, Sheard MA, Malvar J, Fernandez GE, et al · · 2019 · cited 59× · PMID 31068371 · DOI 10.1158/1078-0432.ccr-18-3358
  6. GVHD Pathogenesis, Prevention and Treatment: Lessons From Humanized Mouse Transplant Models.
    Hess NJ, Brown ME, Capitini CM. · · 2021 · cited 47× · PMID 34394131 · DOI 10.3389/fimmu.2021.723544
  7. Interferon Gamma Induces Changes in Natural Killer (NK) Cell Ligand Expression and Alters NK Cell-Mediated Lysis of Pediatric Cancer Cell Lines.
    Aquino-López A, Senyukov VV, Vlasic Z, Kleinerman ES, et al · · 2017 · cited 46× · PMID 28428785 · DOI 10.3389/fimmu.2017.00391
  8. Improving natural killer cell cancer immunotherapy.
    Berrien-Elliott MM, Romee R, Fehniger TA. · · 2015 · cited 37× · PMID 26414502 · DOI 10.1097/mot.0000000000000243

Verify or expand the search:

Other trials of Aldesleukin

Trials testing the same drug.

Other recruiting trials for Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Currently open trials in the same condition.

Other M.D. Anderson Cancer Center trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01823198.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing