Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Other - Standard of Care Consolidation (HCT)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT); HMA-based induction subjects: Are candidates for (as determined by the investigator) and receive HCT

Other - Standard of Care Consolidation (cytarabine-based chemo)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT)

Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1.

Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria:

* Lack the immunophenotype of interest,
* Cytarabine based induction subjects: Are not candidates for \[as determined by the investigator (e.g. unfit or refusal)\] and do not receive consolidation therapy (cytarabine-based chemotherapy or HCT)
* HMA-based induction subjects: Are not candidates for \[as determined by the investigator (e.g. unfit, lack of donor, refusal)\] and do not receive HCT

Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy.

HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT.

Allogeneic HCT

Cytarabine-based consolidation chemotherapy

Consolidation chemotherapy

Michael Grunwald, M.D.

Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) following induction chemotherapy. However, a large majority subsequently relapse and succumb to the disease. Currently, cytogenetics and molecular aberrations are the best prognostic indicators; however, these factors cannot prognosticate accurately for individual patients. Overall, the majority of patients with favorable or intermediate-risk AML will experience relapse. Prognosis after relapse is dismal with a five-year overall survival rate of less than 10%. A leukemia stem cell (LSC) paradigm may explain this failure of CR to reliably translate into cure. This study is undertaken to determine whether the presence of LSCs has prognostic value as well as to determine whether the presence of LSCs has predictive value. This study has an observational component, whereby we intent evaluate whether the presence or absence of LSCs is prognostic. This study also has an interventional component in which it uses LSC status to determine whether favorable and intermediate risk AML patients in CR receive consolidation with chemotherapy or allogeneic HCT.

Leukemia Stem Cell Detection in Acute Myeloid Leukemia

Comparison of 2 year RFS in patient with detectable LSCs in the marrow at the end of consolidation to the 2 year RFS of patients without detectable LSCs. IWG Criteria (Cheson 2003) was utilized to classify relapse, with relapse defined as ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease, or disease presence determined by a physician upon clinical assessment.

Wake Forest University Health Sciences

Both cytarabine-based consolidation chemo and HCT are considered standard of care for this disease population. With the exception of GVHD, an event of clinical interest, adverse events experienced by the subjects were not recorded in the dataset or included in the safety analysis. Each occurrence of GVHD, in evaluable subjects who received HCT, was graded by the investigator according to accepted institutional practice: CIBMTR grading for Acute GVHD; NIH Consensus criteria for Chronic GVHD.

Standard of Care Consolidation (HCT)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT); HMA-based induction subjects: Are candidates for (as determined by the investigator) and receive HCT

Allogeneic HCT: Allogeneic HCT

Evaluable Cohort - Transplant Arm

Standard of Care Consolidation (cytarabine-based chemo)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT)

Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy

Evaluable Cohort - Consolidation Chemo Arm

Observational Cohort 1

Observational Cohort 2

Standard of Care Consolidation (HCT)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT); HMA-based induction subjects: Are candidates for (as determined by the investigator) and receive HCT

Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

AML risk level is determined from bone marrow biopsy performed at AML diagnosis

* Unfavorable: complex karyotype (≥3 clonal chromosomal abnormalities); monosomal karyotype; -5 or 5q-; -7 or 7q-; 11q23 \[non t(9;11)\]; inv(3) or t(3;3); t(6;9); t(9;22); normal cytogenetics with FLT3-ITD mutation, therapy-related AML, or AML from myelodysplastic syndrome or myeloproliferative neoplasm
* Favorable: t(8;21); inv(16) and/or t(16;16), or normal cytogenetics with NPM1 and/or dual CEBPA mutations without FLT3-ITD mutation
* Intermediate: not meeting favorable or unfavorable definitions.

AML Risk Level (prior to induction)

LSC0: Diagnostic bone marrow sample or peripheral blood sample that the leukemia stem cell assay is performed on. LSC0 occurs prior to induction therapy for diagnostic purposes and identifies the subject's immunophenotype at diagnosis.

Immunophenotype at LSC0

LSC0: Diagnostic bone marrow sample or peripheral blood sample that the leukemia stem cell assay is performed on. LSC0 occurs prior to induction therapy for diagnostic purposes.

LSC0 Status (prior to induction)

Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point)

Deletion 5 or 5q

Deletion 7 or 7q

KNMT2A

inv(3) or t(3;3)

t(6;9)

t(9;22)

t(8;21)

inv(16 or t(16;16)

Plus 8

Plus 21

t(9;11)

LSC1: Bone marrow sample that the post-induction leukemia stem cell (LSC) assay is performed on. LSC1 occurs following induction therapy and at the time of complete remission assessment (End of Induction visit).

LSC1 Status (post induction, at enrollment)

Dr. James Symanowski; Chair, Department of Cancer Biostatistics

Of the subjects enrolled in the evaluable cohort (either allo HCT or consolidation chemotherapy), those who had leukemia stem cells detected post-consolidation. Note, eLSC indicates the time point after consolidation.

eLSC+ (Evaluable Cohort)

Of the subjects enrolled in the evaluable cohort (either allo HCT or consolidation chemotherapy), those who had leukemia stem cells not detected post-consolidation. Note, eLSC indicates the time point after consolidation.

eLSC- (Evaluable Cohort)

The primary efficacy analyses will be conducted on the subset of subjects who were included in the evaluable cohort (HCT or chemo treatment arm) and who also had a successful/interpretable end of consolidation eLSC assay. This excludes subjects in OC1 and 2, as they did not achieve CR to induction or did not have the immunophenotype of interest.

2 Year Relapse Free Survival (RFS)

Standard of Care Consolidation (HCT)

Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:

1. Complete remission (CR1) from standard cytarabine or HMA-based induction therapy per standard clinical criteria (Cheson Criteria)
2. Have confirmed presence of CD34+CD38-ALDHint population by flow cytometry at the diagnostic LSC assay (LSC0)
3. Cytarabine-based induction subjects: Are candidates for (as determined by the investigator) and receive consolidation therapy (cytarabine-based chemotherapy or HCT); HMA-based induction subjects: Are candidates for (as determined by the investigator) and receive HCT

Allogeneic HCT

Overall Study

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Molgramostim

Sargramostim

Daunorubicin

Immunoglobulins

Busulfan

Gemtuzumab

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts.

The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts.

The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts.

The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts.

The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count \> 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available.

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count \> 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available.

sargramostim

busulfan

cyclophosphamide

cytarabine

gemtuzumab ozogamicin (GO)

Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.

Autologous hematopoietic cell transplantation

Autologous HCT

Allogeneic hematopoietic cell transplantation

Hugo F. Fernandez, MD

RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.

OBJECTIVES:

* To compare the overall survival (OS) between two induction regimens (standard versus dose intense daunorubicin and cytarabine) in patients with de novo AML.
* To compare disease-free survival (DFS) between two consolidation regimens.
* To compare overall survival between two consolidation regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to induction therapy (standard-dose daunorubicin vs high-dose daunorubicin).

* Induction therapy: Patients are randomized to 1 of 2 induction arms.

  * Standard: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7.
  * High dose: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I.

Patients in both arms may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. The second course is administered as in arm I to all patients. Patients who don't achieve CR after 2 courses of induction therapy are removed from study.

Patients who achieve CR after induction therapy proceed to post-remission therapy with EITHER allogeneic transplantation only (on or off study) OR consolidation therapy and autologous transplantation (on study), according to risk status and donor status.

Patients who are considered at intermediate or high risk for relapse (unfavorable cytogenetics/high WBC) and have a suitable related donor undergo an allogeneic transplantation. Patients with intermediate-risk cytogenetics, WBC no greater than 100,000/mm\^3, and appropriate donors have the option of undergoing allogeneic transplantation.

* Allogeneic transplantation: Within 1-3 months after recovery from induction therapy, patients receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 4 hours on days -3 and -2. Allogeneic bone marrow or peripheral blood stem cells (PBSCs) are infused on day 0. Patients receive graft-vs-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1-4 hours beginning on day -1 and then orally (when tolerated) twice daily until day 180. Alternatively, patients may receive tacrolimus IV over 24 hours beginning on day -1 and then orally twice daily until day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Patients who do not meet the criteria for allogeneic transplantation (i.e., are favorable risk or do not have a matching related donor) or who opt not to undergo allogeneic transplantation proceed to consolidation therapy followed by randomization to 1 of 2 autologous transplantation arms.

* Consolidation therapy: Beginning 2-8 weeks after recovery from induction therapy, patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. A second course is administered 3 weeks after blood recovery. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days and then autologous PBSCs are harvested by leukapheresis.
* Autologous stem cell transplantation: Patients are randomized to 1 of 2 autologous transplantation arms.

  * Arm I: Within 1 month after PBSC collection, patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then undergo autologous PBSC transplantation on day 0. Patients receive sargramostim (GM-CSF) or G-CSF IV or SC beginning on day 0 and continuing until blood counts recover.
  * Arm II (closed to accrual as of 10/4/2007): Within 2-4 weeks after PBSC collection, patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover. Within 2-3 weeks after blood count recovery, patients receive conditioning and undergo autologous PBSC transplantation as in arm I.

Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months for up to 7 years.

ACTUAL ACCRUAL: A total of 657 patients were accrued for this study.

Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia

A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation

Overall survival is defined as the time from randomization in the induction phase to death.

Disease-free survival is defined from the time of the confirmation of a complete remission via biopsy to the relapse of the disease.

Overall survival is defined as the time from randomization in the consolidation phase to death.

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Conditioning/Transplant:

Patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive sargramostim (GM-CSF) or filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 0 and continuing until blood counts recover.

Standard Daunorubicin (Induction Therapy)

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I. Patients may receive a second course of induction therapy if CR is not achieved after the first course. The second course is administered as in arm I.

Conditioning/Transplant:

Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover. Within 2-3 weeks after blood count recovery, patients receive conditioning and undergo autologous PBSC transplantation as in arm I.

High Dose Daunorubicin (Induction Therapy)

Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7.

Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I. Patients may receive a second course of induction therapy if CR is not achieved after the first course. The second course is administered as in arm I.

Statistician

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Patients with CR received consolidation treatment thereafter.

Standard Daunorubicin

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Patients with CR received consolidation treatment thereafter.

High-dose Daunorubicin

All randomized patients are included in the analysis (intention-to-treat).

Overall Survival (Induction Phase)

Patients with CR in the induction phase were randomized to receive autologous HCT or GO/autologous HCT.

Go/Autologous HCT

Only 270 patients who were randomized in the consolidation phase are included in the analysis.

Disease-free Survival (Consolidation Phase)

Overall Survival (Consolidation Phase)

Standard Daunorubicin Then Autologous HCT

High-dose Daunorubicin Then Autologous HCT

Standard Daunorubicin Then GO/Autologous HCT

High-dose Daunorubicin Then GO/Autologous HCT

Standard Daunorubicin Then Allogeneic HCT or no Consolidation

High-dose Daunorubicin Then Allogeneic HCT or no Consolidation

Induction

Conditioning/Transplant

Nervous System Diseases

Skin and Connective Tissue Diseases

Sarcoma

Brain Neoplasms

Osteosarcoma

Central Nervous System Neoplasms

Neuroblastoma

Sarcoma, Ewing

Rhabdomyosarcoma

Nervous System Neoplasms

Neoplasms, Connective and Soft Tissue

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Immunomodulating Agents

Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant.

Donor NK Cell Infusion

Monica Thakar, MD

The investigators hypothesize that this Phase 2 cellular and adoptive immunotherapy study using human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) followed by an early, post-transplant infusion of donor natural killer (NK) cells on Day +7 will not only be well-tolerated in this heavily-treated population (safety), but will also provide a mechanism to treat high-risk solid tumors, leading to improved disease control rate (efficacy). Disease control rate is defined as the combination of complete (CR) and partial (PR) response and stable disease (SD). The investigators further propose that this infusion of donor NK cells will influence the development of particular NK and T cell subtypes which will provide immediate/long-term tumor surveillance, infectious monitoring, and durable engraftment.

Patients with high-risk solid tumors (Ewings Sarcoma, Neuroblastoma and Rhabdomyosarcoma) who have either measurable or unmeasurable disease and have met eligibility will be enrolled on this trial for a goal enrollment of 20 patients over 4 years.

Patients will receive a reduced-intensity conditioning regimen for 6 days that consists of Fludarabine 150 mg/m2, Cyclophosphamide 29 mg/kg, and 3 Gy total body irradiation (TBI), followed by HLA-haploidentical marrow from a family member on Day 0. On Days +3 and +4, Cyclophosphamide 50 mg/kg will be infused for selective in vivo T cell depletion. Additional post-grafting immune suppression will consist of mycophenolate mofetil and either tacrolimus or sirolimus.

Non-mobilized peripheral blood mononuclear cells will be collected from donors on Day +6, from which NK cells will be selected and infused into patients on Day +7.

Patients will be monitored for any transplant-related complications and will undergo disease monitoring every three months for the first two years post-transplant. Research studies will be conducted to follow the patient's immune status and quality of life post-transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Leukemia Stem Cell Detection in Acute Myeloid Leukemia	NCT02927938	Acute Myeloid L...	Allogeneic HCT Consolidation c...	18 Years -	Wake Forest University Health Sciences
Leukemia Stem Cell Detection in Acute Myeloid Leukemia	NCT02927938	Acute Myeloid L...	Allogeneic HCT Consolidation c...	18 Years -	Wake Forest University Health Sciences
Leukemia Stem Cell Detection in Acute Myeloid Leukemia	NCT02927938	Acute Myeloid L...	Allogeneic HCT Consolidation c...	18 Years -	Wake Forest University Health Sciences
Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia	NCT00049517	Leukemia	sargramostim busulfan cyclophosphamid... cytarabine gemtuzumab ozog... Daunorubicin Autologous HCT Allogeneic HCT	16 Years - 60 Years	Eastern Cooperative Oncology Group
Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors	NCT02100891	Ewing Sarcoma Neuroblastoma Rhabdomyosarcom... Osteosarcoma CNS Tumors	Allogeneic HCT Donor NK Cell I...	-	Medical College of Wisconsin

Spots Global Cancer Trial Database for allogeneic hct