Background
Case presentation
January 2017: Skin biopsy showed LCH | |
February 2017: Progressive nausea/diarrhea, weight loss | |
March 2017: EGD - herpes esophagitis, Barrett’s esophagus, Helicobacter pylori gastritis, Langerhans cell sarcoma in stomach/duodenum Acyclovir full dose, triple therapy (could not tolerate) | |
April 2017: Persistent nausea/emesis, weight loss EGD: Resolved herpes esophagitis, Barrett’s esophagus, persistent gastritis, Langerhans cell sarcoma in stomach/duodenum PET/CT: Diffuse uptake in bone marrow, and GI tract Brain MRI (−) Bone MRI: Diffuse marrow changes, no bone lesions Normal CBC, LDH BMBx (−) | |
May 2017: Cytarabine 100 mg/m2/d × 5 d | |
July 2017: EGD/colonoscopy post C3 - still significant erythema, biopsy (+) | |
August 2017: Improved but persistent symptoms Skin biopsy - LCH | |
September 2017: C6 - switch to every 2 weeks | |
October 2017: BMBx post C7 – No evidence of disease, dyspoiesis likely from chemo, (−) AML FISH and myeloid NGS | |
November 2017: Right posterior cerebral artery [PCA] thrombus s/p TPA Circulating blasts: BMBx - acute monoblastic leukemia Karyotype: 45,XY,der(13;14)(q10;q10) 45,X,der(Y)t(Y;?)(q11.2;?), sl, der(1)t(1;9)(p10;q10), der(8)t(1;8)(q10;p10), del(10)(p11.2) AML NGS (−), FISH (−) | |
November 2017: 7 + 3 - D15: Recurrent skin lesions BMBx - persistent AML Karyotype: 45,XY,der(13;14)(q10;q10) Skin lesion: Leukemia cutis with LCH (+) AML NGS PTPN11 mutation FISH (+) homozygous del 9p21 | |
December 2017: CLAG-M - diplopia on D1 (+) MRI and LP for CSF involvement LP with IT chemo 2x/week × 6 - (−) first LP Recovery marrow - CR | |
January 2018: HiDAC 3 g/m2 x C1 + IT | |
February 2018: Cytarabine 2 g/m2 + cladribine 5 mg/m2 + mitoxantrone 10 mg/m2 + IT | |
March 2018: MTX 5 g/m2 + cytarabine 3 g/m2 as a bridge to transplant due to new skin lesions + IT |
Discussion and conclusions
Study title (ClinicalTrials.gov identifier) | Interventions | Study design | Locations |
---|---|---|---|
AraC for Newly Diagnosed Adult Langerhans Cell Histiocytosis (NCT04121819) | Drug: Cytarabine | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Peking Union Medical College Hospital, Beijing, China |
Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders (NCT02425904) | Drug: Clofarabine | Allocation: Nonrandomized Intervention model: Single- group assignment Masking: None (open label) Primary purpose: Treatment | Phoenix Children’s Hospital, Phoenix, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA Children’s Hospital of Los Angeles, Los Angeles, CA, USA (and 12 more) |
LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis (NCT02205762) | Drug: Prednisone Drug: Vinblastine Drug: Mercaptopurine (and 6 more) | Allocation: Randomized intervention model: Parallel assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Phoenix Children’s Hospital, Phoenix, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 28 more) |
Thalidomide, Cyclophosphamide and Dexamethasone for Recurrent/Refractory Adult Langerhans Cell Histiocytosis (NCT04120519) | Drug: Thalidomide combined with dexamethasone and cyclophosphamide | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Peking Union Medical College Hospital, Beijing, China |
Vinblastine/Prednisone Versus Single Therapy With Cytarabine for Langerhans Cell Histiocytosis (LCH) (NCT02670707) | Drug: Cytarabine Drug: Vinblastine/prednisone | Allocation: Randomized intervention model: Parallel assignment masking: None (open label) Primary purpose: Treatment | Texas Children’s Hospital, Houston, TX, USA |
Denosumab for the Treatment of Adult LCH (NCT03270020) | Drug: Denosumab 70 mg/ml (XGEVA; Amgen, Charlotte, NC, USA) | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | 251 Hellenic Air Force and VA Athens General Hospital, Department of Endocrinology, Attiki, Greece |
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NCT04079179) | Drug: Cobimetinib | Allocation: Nonrandomized intervention model: Parallel assignment Masking: None (open label) Primary purpose: Treatment | NACHO Consortium, Memphis, TN, USA Texas Children’s Hospital, Houston, TX, USA |
A Combination of Vemurafenib, Cytarabine and 2-chlorodeoxyadenosine in Children With LCH and BRAF V600E Mutation (NCT03585686) | Drug: Vemurafenib Drug: Cytarabine Drug: 2-Chlorodeoxyadenosine | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation |
Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH) (NCT04100408) | Other: Biospecimen collection Other: Laboratory biomarker analysis Other: Questionnaire administration | Observational model: Family-based Time perspective: Prospective | Baylor College of Medicine/Dan L. Duncan Comprehensive Cancer Center at Baylor St. Luke’s Medical Center, Houston, TX, USA |
A Study of Memory, Thinking, and Brain Imaging in Adults With Histiocytosis (NCT03127709) | Behavioral: Trail Making Test parts A and B Behavioral: Brief Test of Attention Behavioral: Symbol Span (and 8 more) | Observational model: Cohort Time perspective: Prospective | Memorial Sloan Kettering Basking Ridge, Basking Ridge, NJ, USA Memorial Sloan Kettering Monmouth, Middletown, NJ, USA Memorial Sloan Kettering Cancer Center @ Suffolk, Commack, NY, USA (and 1 more) |
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (NCT03155620) | Procedure: Biopsy Procedure: Biospecimen collection Drug: Ensartinib (and 12 more) | Allocation: Nonrandomized Intervention model: Parallel assignment Masking: None (open label) Primary purpose: Screening | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Phoenix Children’s Hospital, Phoenix, AZ, USA (and 143 more) |
Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial) (NCT03526250) | Other: Laboratory biomarker analysis Drug: Palbociclib Other: Pharmacological study | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Phoenix Children’s Hospital, Phoenix, AZ, USA (and 93 more) |
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) (NCT03698994) | Other: Pharmacokinetic study Drug: Ulixertinib | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 94 more) |
Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial) (NCT03233204) | Drug: Olaparib | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 102 more) |
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial) (NCT03210714) | Drug: Erdafitinib Other: Laboratory biomarker analysis Other: Pharmacological study | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 103 more) |
PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial) (NCT03213678) | Other: Laboratory biomarker analysis Other: Pharmacological study Drug: Samotolisib | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 104 more) |
Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial) (NCT03213665) | Other: Laboratory biomarker analysis Drug: Tazemetostat | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Phoenix Children’s Hospital, Phoenix, AZ, USA (and 106 more) |
Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial) (NCT03213704) | Drug: Larotrectinib Drug: Larotrectinib sulfate | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 105 more) |
CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation (NCT01966367) | Biological: CD34 stem cell selection therapy | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | NewYork-Presbyterian Morgan Stanley Children’s Hospital, Columbia University, New York, NY, USA |
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial) (NCT03220035) | Other: Laboratory biomarker analysis Drug: Vemurafenib | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Children’s Hospital of Alabama, Birmingham, AL, USA Cardon Children’s Medical Center, Mesa, AZ, USA Arkansas Children’s Hospital, Little Rock, AR, USA (and 103 more) |
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies (NCT01652092) | Drug: Alemtuzumab 0.3 mg Drug: Cyclophosphamide Drug: Busulfan (and 6 more) | Allocation: Nonrandomized intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA |
Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations (NCT02124772) | Drug: Trametinib Drug: Dabrafenib | Allocation: Nonrandomized Masking: None (open label) Primary purpose: Treatment | Novartis Investigative Site, Phoenix, AZ, USA Novartis Investigative Site, San Francisco, CA, USA Novartis Investigative Site, Baltimore, MD, USA (and 13 more) |
Pediatric Long-Term Follow-up and Rollover Study (NCT03975829) | Drug: Dabrafenib Drug: Trametinib | Intervention model: Single-group assignment Masking: None (open label) Primary purpose: Treatment | |
CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant (NCT02061800) | Device: CliniMACS CD34+ reagent system (Miltenyi Biotech, Bergisch Gladbach, Germany) Drug: Thiotepa Drug: Cyclophosphamide (and 6 more) | Allocation: Nonrandomized Intervention model: Parallel assignment Masking: None (open label) Primary purpose: Treatment | Columbia University Medical Center, New York, NY, USA |