Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

All Drugs and Chemicals

Antibodies

Vaccines

Immunoglobulins

Heptavalent Pneumococcal Conjugate Vaccine

Richard A Zuckerman, MD

The purpose of this study is to determine if higher absolute lymphocyte count in the infused stem cell autograft (A-ALC) will lead to an improved antibody response to post-transplant immunization with Pneumococcal Conjugate Vaccine and permit effective immunization at 6 months post-transplant in lymphoma patients receiving Autologous Peripheral Blood Stem Cell Transplantation.

Infectious diseases remain a leading cause of morbidity and mortality in patients who receive high-dose chemotherapy followed by Autologous Peripheral Blood Stem Cell Transplantation (APBSCT). Infectious disease complications of transplantation might be reduced by effective post-transplant immunization but reconstitution of the immune system may take months to years after transplantation and responses to immunization are often attenuated in this setting. Correlates of improved immune reconstitution and response to immunization after transplantation would be important to identify. It has been recently shown that higher absolute lymphocyte count in the infused stem cell autograft (A-ALC) and higher ALC at day +15 after stem cell infusion (ALC-15) are independently associated with improved overall survival after APBSCT. The mechanism of this association is unclear, but this finding suggests that improved immune responses to immunization might also be achieved with this approach making it possible to immunize at 6 months instead of at one year. This hypothesis has never been evaluated.

Survival following APBSCT is improved with a higher A-ALC and ALC-15. It is postulated that the higher lymphocyte numbers correlate with improved immune surveillance and destruction of minimal residual disease. Thus, one must consider the probability higher A-ALC will confer improved response to T-cell dependent immunization early after transplant.

Higher Infused Lymphocyte Counts Improve Antibody Response to Immunization After Autologous Stem Cell Transplantation

To assess the antibody response to Prevnar® and its correlation to autograft absolute lymphocyte count (A-ALC).

Dartmouth-Hitchcock Medical Center

Director, Transplant Infectious Disease Program

Heart and Blood Diseases

Nutritional and Metabolic Diseases

Leukemia

Multiple Myeloma

Neoplasms, Plasma Cell

Amyloidosis

Hodgkin Disease

Paraproteinemias

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Proteostasis Deficiencies

Metabolic Diseases

Hodgkin Lymphoma

Antineoplastic Agents

Analgesics

Molgramostim

Sargramostim

Interleukin-2

Immune Mobilization of Autologous Peripheral Blood Stem Cells Using Interleukin-2 and GM-CSF

GM-CSF (Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor) The dose and duration of GM-CSF (7.5 mcg/kg/day) was selected. If used alone, this dose and duration would result in effective mobilization. GM-CSF will be started on Day #7 and will continue until completion of leukapheresis.

G-CSF will be started (5mcg/kg/d) on Day #7 and will be given each morning. G-CSF will continue until completion of leukapheresis.

GM-CSF

IL-2 dose escalation: IL-2 will be administered as a single daily subcutaneous injection each evening until completion of leukapheresis.

Escalation of the dose of IL-2 will be performed using the below schema with the following levels. Patients will be started on Level 1. (Level 0 is included since, if toxicity is meet in Level 1, the dose will be decreased to Level 0).

Level 0 - 3 x 105 i.u./m2/day for 11 days Level 1 - 6 x 105 i.u./m2/day for 11 days Level 2 - 1 x 106 i.u. /m2/day for 11 days as above Level 3 - 1.5 x 106 i.u. /m2/day for 11 days as above Level 4 - 2 x 106 i.u. /m2/day for 11 days as above

IL-2

Kenneth R Meehan, MD

We postulate that the combination of IL-2 and GM-CSF immunotherapy will efficiently mobilize autologous peripheral blood stem cells and activated immune effector cells in patients with a hematologic malignancy. These activated effector cells will improve the immune function of the graft. These hypotheses will be tested using this proposed clinical trial to mobilize autologous peripheral blood stem cells pre-transplantation.

Director, Bone Marrow Transplant Program

Symptoms and General Pathology

Syndrome

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Immunomodulating Agents

Infusion of autologous CIK cells in study group. There is only one arm to this study

Autologous CIK cells will be infused at timed intervals after autologous transplant for AML for group 1 patients, and with or without some cytoreduction treatment for group 2 patients

Infusion of autologous CIK cells

Yeh-Ching Linn, MBBS, MRCP

A phase I/II study to explore the feasibility and efficacy of autologous CIK cells in patients with acute myeloid leukemia (AML)/ high grade myelodysplastic syndrome (MDS)

1. Group 1: As adjuvant therapy in minimal residual disease state after autologous PBSCT.
2. Group 2: As an adoptive immunotherapy in untreated disease state when conventional therapy with curative intent is not applicable

This is a Phase I /II study on the feasibility / efficacy of adoptive immunotherapy with autologous CIK cells for the following 2 groups of patients who have AML or high grade MDS :

1. Group 1 patients in minimal residual disease state post autologous peripheral blood stem cell transplant ( PBSCT ), and
2. Group 2 patients with untreated high grade MDS or AML, who are not fit for standard curative intent chemotherapy.

The CIK cells will be generated by leukapheresis from patients and cultured in GMP facilities. Four repeated infusions will be given for a target dose of 1x10e10 T cell per infusion.

Efficacy will be assessed by

1. Disease free survival compared to historical control in group 1 given CIK cells post autologous PBSCT as adjuvant immunotherapy (n=20 over 3 years), and
2. Effect on the peripheral or marrow leukemia cell load in group 2 patients given CIK cells as alternative therapy in place of chemotherapy (n=10).

Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome

National Medical Research Council (NMRC), Singapore

Singapore General Hospital

Anti-Infective Agents

Cytarabine

Idarubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Induction (idarubicin, cytarabine), first consolidation (high dose cytarabine), risk- stratification: allogeneic matched related or unrelated donor transplant vs. consolidation courses.

12 mg/m2/day; intravenous, administration at induction phase, days 1 to 3.

200mg/m2/day, intravenous at induction phase; days 1-7.

- High dose during consolidation phase. In patients up to 60 years 3g/m2/12hours days 1,3,5, and patients 60 to 70 years: 1.5g/m2/12hours days 1,3,5.

Ara-C

* Administration at induction phase to remission days 1 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatment arises 30x10e9/L.
* Administration at consolidation phase day 7.

G-CSF

To be performed in patients in the intermediate or adverse risk groups.

Allogeneic matched or unrelated donor transplant.

To be considered in patients in the intermediate risk group without an available allogeneic donor and negative measurable residual disease, per center decision.

Autologous peripheral blood stem cell transplant

To be performed either with molecular monitoring or, if not applicable, by flow cytometry. Pre-stablished cut-off values are defined for decision-making.

Measurable residual disease

Jorge Sierra, Prof, MD

Jordi Esteve, MD, PhD

The AML-12 study investigates the efficacy and toxicity of standard induction chemotherapy with idarubicin and cytarabine (IC) with G-CSF priming followed by a risk-adapted post remission therapy for patients up to the age of 70 diagnosed with de novo acute myeloid leukemia (AML).

Modifications from the previous protocol AML-03 (NCT01723657) include removal of etoposide in induction, limitation of the GCSF priming to the induction phase and categorization of post remission therapy (stem cell transplant or 2 high dose cytarabine consolidations) according to diagnostic genetics as well as post-remission clearance of measurable residual disease.

The aims of these modifications are to improve the overall survival and leukemia free survival of acute myeloid leukemia patients with a risk-adapted approach.

Induction chemotherapy: Idarubicin (12mg/m2/day intravenous, days 1-3), Low-dose cytarabine (200mg/m2/day, intravenous in continuous infusion, days 1-7) and G-CSF priming 150mcg/m2/day, subcutaneous from day 0 to the last day of chemotherapy if white blood cell count (WBC) \<30x10E9/L.

This induction chemotherapy can be repeated twice in the case of partial response (PR) to achieve complete response (CR).

Once CR is achieved (with one or two induction cycles), all patients receive a consolidation course with high-dose cytarabine (3000mg/m2/12h days 1, 3 and 5) and pegfilgrastim 6mg on day 6.

After this, patients will be allocated to the different risk groups as follows:

* Favorable risk group \[patients with t(8;21)(q22;q22)/RUNX1/RUNX1T1, inv(16)(p12;q22) or t(16;16)/CBFB/MYH11; Intermediate risk cytogenetics (MRC 2010) and NPM1 mutation with FLT3 wild type or low ratio of FLT3 internal tandem duplication (ITD)/wild type (\<0.5); or CEBPA biallelic mutation\]. Patients in this group will receive 2 additional courses of consolidation therapy
* Intermediate risk group \[Intermediate risk cytogenetics (MRC 2010) without NPM1 mutations, FLT3-ITD, or CEBPA biallelic mutation\]. Patients in this group receive an allogeneic stem cell transplant in first CR. Patients without an available donor can be autografted per center decision
* Adverse risk group \[Adverse risk cytogenetics (MRC 2010), intermediate cytogenetics with FLT3-ITD without NPM1 mutation or NPM1-FLT3-ITD high ratio or MLL rearrangement; any favorable or intermediate risk patients with positive MRD following 1 (intermediate) or 2 (favorable) consolidation courses\]. Intention to treat of those patients is allogeneic stem cell transplant from any source.

Risk-adapted Therapy for Primary Acute Myeloid Leukemia

Risk-adapted Therapy for Primary Acute Myeloid Leukemia (AML) in Adult Patients up to 70 Years Old

Analyze the efficacy and toxicity of the current doses of IC (Idarubicin and cytarabine) with G-CSF priming to achieve complete remission in patients tih AML up to 70yo.

Analyze the disease free survival in the whole cohort of AML patients.

Analyze the relapse rate of all patients achieving remission with intensive induction followed by risk-adapted consolidation strategies.

Increase the number of patients who complete all treatment phases

Evaluate the feasibility of the consolidation treatments in the different risk groups by comparison of overall survival (OS), RR and DFS.

Survival outcomes in positive vs negative MRD patients. Number of patients with modified risk due to positive MRD.

Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Lymphoma, Non-Hodgkin

Antihypertensive Agents

Vasodilator Agents

Vasoconstrictor Agents

Angiotensin I (1-7)

Angiotensin II

Angiotensinogen

300mcg/kg/day administered subcutaneously up to 28 days

300mcg/kg/day, administered subcutaneously for up to 28 days

TXA127

300mcg/kg/day administered subcutaneously for up to 28 days

Placebo

Michael Schuster, MD

The purpose of this study is to determine the safety and effectiveness of TXA127 in accelerating the time it takes for patients to recover their platelet counts following a Autologous Peripheral Blood Stem Cell transplant.

* This is a randomized, double-blind (Investigator and Study Subject), placebo-controlled study.
* The conditioning regimen and mobilization agents used will be up to the discretion of the Study Center Investigator

Acceleration of Platelet Recovery Following Autologous Peripheral Blood Stem Cell Transplant (PBSC) in Hodgkin, Non-Hodgkin Lymphoma or Multiple Myeloma Patients

Phase II Study Evaluating the Safety and Efficacy of TXA127 in the Acceleration of Platelet Recovery Following Autologous Peripheral Blood Stem Cell Transplant in Patients With Hodgkin Lymphoma, Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Limited Reinfusion of CD34+ Cells

Evaluate the effectiveness of TXA127 in accelerating the time to initial platelet recovery following PBSC transplant with a limited number of CD34+ cells, defined as CD34+ cell concentrations ≥1.5 x 106 and ≤5.0 x 106 CD34+ cells/kg. Platelet recovery is defined as that day the subject achieves a post-nadir platelet count of ≥20 x 109/L with no platelet transfusion in the prior 7 days.

Evaluate the safety of TXA127 administration following PBSC transplant

Determine the effectiveness of TXA127 in accelerating the days to initial neutrophil recovery (ANCs \> 0.5 x 10⁹/L)

Evaluate the incidence of mucositis Grade 3/4

Evaluate the effect of TXA127 in reducing the number of days of febrile neutropenia (fever and ANC \<0.5 x 109/L)

Evaluate the effect of TXA127 in reducing the number of platelet transfusions needed

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Higher Infused Lymphocyte Counts Improve Antibody Response to Immunization After Autologous Stem Cell Transplantation	NCT00889278	Lymphoma		18 Years -	Dartmouth-Hitchcock Medical Center
Immune Mobilization of Autologous Peripheral Blood Stem Cells Using Interleukin-2 and GM-CSF	NCT00952237	Non-Hodgkin's L... Hodgkin's Disea... Multiple Myelom... Other Plasma Ce... Leukemia	GM-CSF IL-2	18 Years -	Dartmouth-Hitchcock Medical Center
Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT00394381	Acute Myeloid L... Myelodysplastic...	Infusion of aut...	12 Years - 75 Years	Singapore General Hospital
Risk-adapted Therapy for Primary Acute Myeloid Leukemia	NCT04687098	Leukemia, Myelo...	Idarubicin Ara-C G-CSF Allogeneic matc... Autologous peri... Measurable resi...	17 Years - 70 Years	Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Acceleration of Platelet Recovery Following Autologous Peripheral Blood Stem Cell Transplant (PBSC) in Hodgkin, Non-Hodgkin Lymphoma or Multiple Myeloma Patients	NCT01121120	Lymphoma, Non-H... Hodgkin Disease Multiple Myelom...	TXA127 Placebo	18 Years -	Tarix Pharmaceuticals
Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT00394381	Acute Myeloid L... Myelodysplastic...	Infusion of aut...	12 Years - 75 Years	Singapore General Hospital
Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT00394381	Acute Myeloid L... Myelodysplastic...	Infusion of aut...	12 Years - 75 Years	Singapore General Hospital
Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT00394381	Acute Myeloid L... Myelodysplastic...	Infusion of aut...	12 Years - 75 Years	Singapore General Hospital
Risk-adapted Therapy for Primary Acute Myeloid Leukemia	NCT04687098	Leukemia, Myelo...	Idarubicin Ara-C G-CSF Allogeneic matc... Autologous peri... Measurable resi...	17 Years - 70 Years	Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Spots Global Cancer Trial Database for autologous peripheral blood stem cell transplant