^
9d
A Phase 1 Trial of CIML NK Cell Infusion for Myeloid Disease Relapse After Hematopoietic Cell Transplantation (clinicaltrials.gov)
P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
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IL2 (Interleukin 2)
|
cyclophosphamide • fludarabine IV • CIML NK
9d
Journal
|
PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SETBP1 (SET Binding Protein 1)
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PTPN11 mutation
10d
Biological Markers of Myeloproliferative Neoplasms in Children, Adolescents and Young Adults. (PubMed, Cancers (Basel))
Although rare, myeloproliferative neoplasms can involve young patients and pose unique challenges for clinicians in diagnosis and therapy. The paper aims to review the biological markers of MPNs in pediatric populations-a particular group of patients that has been poorly studied due to the low frequency of MPN diagnosis.
Review • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)
24d
Constitutional Mosaic Pericentromeric Trisomy 8 in a Female Patient With Aplastic Anemia. (PubMed, Am J Med Genet A)
These regions overlap with 13 published cases (12 papers), of which three displayed hematologic disorders, including neutropenia and juvenile myelomonocytic leukemia. Our case underscores the 8p12q11.21 region as a potential causal region for aplastic anemia, emphasizing the need for further investigation of this patient for possible progression to hematologic malignancy.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • KAT6A (Lysine Acetyltransferase 6A) • IKBKB (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Beta)
28d
LIMBER: Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (clinicaltrials.gov)
P1, N=231, Recruiting, Incyte Corporation | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Metastases
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Jakafi (ruxolitinib) • INCB57643
2ms
A prospective clinical study to evaluate the efficacy of dexitabine in maintenance therapy after hematopoietic stem cell transplantation in juvenile myelomonocytic leukemia (ChiCTR2400091166)
P=N/A, N=40, Not yet recruiting, The Seventh Affiliated Hospital, Sun Yat-sen University; The Seventh Affiliated Hospital, Sun Yat-sen University
New trial
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KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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KRAS mutation • NRAS mutation • NF1 mutation • PTPN11 mutation • CBL mutation
2ms
Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG. (PubMed, Immunol Med)
The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.
Journal
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CSF2 (Colony stimulating factor 2)
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CSF2 elevation
2ms
ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)
P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025
Trial completion date
|
NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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NF1 mutation • RAS mutation • PTPN11 mutation • CBL mutation
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Mekinist (trametinib) • omipalisib (GSK2126458)
3ms
Enrollment closed • Enrollment change
|
Rituxan (rituximab) • cyclophosphamide • Blincyto (blinatumomab) • sirolimus • melphalan • fludarabine IV • mesna • thiotepa • Neupogen (filgrastim)
3ms
SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects with MDS or AML (clinicaltrials.gov)
P1, N=160, Active, not recruiting, Shattuck Labs, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Apr 2025 --> Nov 2024
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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TP53 (Tumor protein P53)
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TP53 mutation
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Venclexta (venetoclax) • azacitidine • SL-172154
3ms
Enrollment change • Trial completion date
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
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SAR443579
3ms
Transient Myeloproliferative Disorder (TMD), Acute Lymphoblastic Leukemia (ALL), and Juvenile Myelomonocytic Leukemia (JMML) in a Child with Noonan Syndrome: Sequential Occurrence, Single Center Experience, and Review of the Literature. (PubMed, Genes (Basel))
After an initial response to antimetabolite therapy (6-mercaptopurine), she underwent haploidentical hematopoietic stem cell transplantation (HSCT) and is currently in complete remission. The goal of this review is to gain insight into the various hematological diseases associated with NS, starting from our unique case.
Review • Journal
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PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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PTPN11 mutation
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mercaptopurine
3ms
A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy (clinicaltrials.gov)
P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Apr 2026 --> Jun 2026 | Trial primary completion date: Apr 2026 --> Jun 2026
Trial completion date • Trial primary completion date • Combination therapy
|
cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)
3ms
CBL mutations in chronic myelomonocytic leukemia often occur in the RING domain with multiple subclones per patient: Implications for targeting. (PubMed, PLoS One)
Furthermore, we noted an increased percentage of CMML CD34+ stem and progenitor cells expressing CD116 and CD131 in all CBL mutant cases and increased CD116 receptor density compared to healthy controls, similar to CMML overall. In summary, our data demonstrate that CBL mutations are associated with distinct molecular and clinical features in CMML and are potentially targetable with CD116-directed immunotherapy.
Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule)
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KRAS mutation • NRAS mutation • TET2 mutation • CBL mutation
3ms
Pitfalls in Diagnosis: JMML versus KMT2A Rearranged Juvenile AML. (PubMed, Case Rep Hematol)
This case highlights the challenges of diagnosing KMT2A-rearranged monocytic AML and the importance of careful morphological assessment in partnership with cytogenetic and molecular diagnostics to distinguish between KMT2A-rearranged AML and JMML. Moreover, the emerging role of molecular monitoring in AML is highlighted.
Journal
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KMT2A (Lysine Methyltransferase 2A)
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KMT2A rearrangement • MLL rearrangement
4ms
Myeloproliferative Neoplasms (MPNs) Patient Registry (clinicaltrials.gov)
P=N/A, N=5000, Recruiting, University Health Network, Toronto | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027
Trial completion date • Trial primary completion date
4ms
Prototypical innate immune mechanism hijacked by leukemia-initiating mutant stem cells for selective advantage and immune evasion in Ptpn11-associated juvenile myelomonocytic leukemia. (PubMed, Res Sq)
Importantly, pharmacological inhibition of S100a9/S100a8 signaling effectively impeded leukemia development from Ptpn11 E76K/+ mutant stem cells. These findings collectively suggest that JMML tumor-initiating cells exploit evolutionarily conserved innate immune and inflammatory mechanisms to establish clonal dominance.
Journal
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PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • S100A8 (S100 Calcium Binding Protein A8) • S100A9 (S100 Calcium Binding Protein A9)
5ms
Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience. (PubMed, Cancers (Basel))
All patients (5/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Among patients who received transplants, 7/13 are alive, and relapse post-transplant occurred in 3/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germline PTPN11 mutations.
Journal • Real-world evidence • Real-world
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NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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azacitidine • mercaptopurine
5ms
Trial initiation date • Combination therapy
|
cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)
5ms
Trial completion date • Trial primary completion date
|
Rituxan (rituximab) • cyclophosphamide • Blincyto (blinatumomab) • sirolimus • melphalan • fludarabine IV • mesna • thiotepa • Neupogen (filgrastim)
5ms
Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov)
P1, N=15, Recruiting, Johns Hopkins All Children's Hospital | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
Trial completion date • Trial primary completion date • Combination therapy
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azacitidine • Zolinza (vorinostat)
5ms
Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss. (PubMed, J Cell Sci)
Knockdown of a BORC complex subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that the BORC complex may be a promising therapeutic target for NF1-deficient tumors.
Journal • Synthetic lethality
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NF1 (Neurofibromin 1)
5ms
Enrollment open
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cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)
6ms
A Phase II Pediatric Study of a Graft-VS.-Host Disease (GVHD) Prophylaxis Regimen With no Calcineurin Inhibitors After Day +60 Post First Allogeneic Hematopoietic Cell Transplant for Hematological Malignancies (clinicaltrials.gov)
P2, N=3, Terminated, St. Jude Children's Research Hospital | N=32 --> 3 | Trial completion date: Apr 2027 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2026 --> May 2024; Principal Investigator left institution
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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Jakafi (ruxolitinib) • cyclophosphamide • fludarabine IV • mesna • thiotepa • busulfan • cyclosporine
6ms
Immunological and hematological findings as major features in a patient with a new germline pathogenic CBL variant. (PubMed, Am J Med Genet A)
Functional studies documented enhanced EGF-induced ERK phosphorylation in transiently transfected COS1 cells. The present findings further support the association of pathogenic CBL variants with immunological and hematological manifestations in the context of a presentation with only minor findings reminiscent of NS or a clinically related RASopathy.
Retrospective data • Journal
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EGF (Epidermal growth factor)
6ms
New P2 trial
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TP53 (Tumor protein P53) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD34 (CD34 molecule)
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dorocubicel (UM171 cell therapy)
6ms
Risk-adapted Donor Lymphocyte Infusion After Allo-HSCT in Children With Hematologic Malignancy (clinicaltrials.gov)
P1/2, N=50, Completed, St. Petersburg State Pavlov Medical University | Active, not recruiting --> Completed
Trial completion
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
7ms
Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov)
P1, N=15, Recruiting, Johns Hopkins All Children's Hospital | Trial completion date: Jun 2024 --> Oct 2024
Trial completion date
|
azacitidine • Zolinza (vorinostat)
7ms
A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)
P1/2, N=58, Recruiting, Therapeutic Advances in Childhood Leukemia Consortium | Not yet recruiting --> Recruiting
Enrollment open • Tumor mutational burden
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
|
KRAS mutation • NRAS mutation • NF1 mutation • RAS mutation
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Mekinist (trametinib) • cytarabine • azacitidine • fludarabine IV
8ms
The elevation of red blood cell distribution width is an independent prognostic factor for juvenile myelomonocytic leukemia. (PubMed, Blood Sci)
RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.
Journal
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PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
|
PTPN11 mutation
9ms
Identifying Potential SOS1 Inhibitors via Virtual Screening of Multiple Small Molecule Libraries against KRAS-SOS1 Interface. (PubMed, Chembiochem)
Comparative analysis of the average binding free energies of these predicted potent compounds with known SOS1 small molecule inhibitors revealed that the identified compounds display similar or even superior predicted binding affinities compared to the known inhibitors. These findings offer valuable insights into the potential of these compounds as candidates for further development as effective anti-cancer agents.
Journal
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
9ms
Journal
|
SH2B3 (SH2B Adaptor Protein 3)
|
SH2B3 alteration
9ms
Enrollment open
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3 mutation • CBL mutation • Chr t(9;11)
9ms
03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov)
P1, N=160, Recruiting, Shattuck Labs, Inc. | N=107 --> 160 | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Feb 2024 --> Apr 2025
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Venclexta (venetoclax) • azacitidine • SL-172154
9ms
HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant (clinicaltrials.gov)
P1, N=24, Suspended, Fred Hutchinson Cancer Center | Trial completion date: Jul 2025 --> Jul 2028 | Trial primary completion date: Oct 2024 --> Oct 2027
Trial completion date • Trial primary completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CD4 (CD4 Molecule)
|
HLA-A*02:01
|
fludarabine IV
10ms
Long-term remission of infantile Takayasu arteritis associated with germline CBL syndrome after allogeneic hematopoietic stem cell transplantation: A case report and literature review. (PubMed, Transpl Immunol)
The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.
Clinical • Observational data • Retrospective data • Review • Journal
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CBL (Cbl proto-oncogene)
10ms
A comprehensive genomic profiling of myeloid malignancies demonstrates mutational spectrum of DNA variants, FLT3-ITDs, and gene fusions (AACR 2024)
The Oncomine Myeloid Assay is a fast, robust, and reproducible solution for comprehensive genomic profiling of myeloid malignancies. We describe the mutational spectrum of DNA variants and RNA fusions in a range of clinical research samples. (For research use only.
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZMYM2 (Zinc Finger MYM-Type Containing 2) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • ANKRD26 (Ankyrin Repeat Domain Containing 26)
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FLT3-ITD mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • FGFR1 fusion
|
Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay
10ms
A predictive classifier of poor prognosis in transplanted patients with juvenile myelomonocytic leukemia: a study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire. (PubMed, Haematologica)
By integrating genetic information with clinical and hematological features, we have devised a predictive classifier. This classifier effectively identifies a subgroup of patients who are at a heightened risk of unfavorable post-transplant outcomes who would benefit novel therapeutic agents and post-transplant strategies.
Journal
|
ASXL1 (ASXL Transcriptional Regulator 1) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1)
|
RAS mutation • ASXL1 mutation • JAK3 mutation
10ms
US Study of ECT-001-CB in Pediatric and Young Adult Patients With High-Risk Myeloid Malignancies (clinicaltrials.gov)
P1/2, N=12, Recruiting, ExCellThera inc. | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2023 --> Jun 2026
Trial completion date • Trial primary completion date
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD34 (CD34 molecule)
|
cyclophosphamide • clofarabine • fludarabine IV • thiotepa • busulfan • dorocubicel (UM171 cell therapy)
11ms
CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT (clinicaltrials.gov)
P=N/A, N=50, Recruiting, Children's Hospital of Philadelphia | N=30 --> 50 | Trial completion date: Jan 2024 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Feb 2025
Enrollment change • Trial completion date • Trial primary completion date
|
cyclophosphamide
11ms
New P1 trial
|
cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)
11ms
A Phase 1 Trial of CIML NK Cell Infusion for Myeloid Disease Relapse After Hematopoietic Cell Transplantation (clinicaltrials.gov)
P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Active, not recruiting --> Enrolling by invitation
Enrollment open
|
IL2 (Interleukin 2)
|
cyclophosphamide • fludarabine IV • CIML NK