Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Infections

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Hodgkin Disease

Leukemia, Prolymphocytic

Preleukemia

Myelodysplastic Syndromes

Lymphoma, B-Cell

Bone Marrow Failure Disorders

Pancytopenia

Burkitt Lymphoma

Hematologic Diseases

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphoma, Non-Hodgkin

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).

Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.

Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.

Total Body Irradiation

Haploidentical stem cell transplant

Claudio Brunstein, MD

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.

Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases

Reduced Intensity Conditioning (RIC) and Transplantation of HLA(Human Leukocyte Antigen)-Haploidentical Related Bone Marrow (Haplo-BM) For Patients With Hematologic Diseases

Percentage of patients that survive 2 years post-transplant

Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10\^8/L for 3 consecutive measurements.

Number of patients with chimerism at day 100, 6 months and 1 year

Masonic Cancer Center, University of Minnesota

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).

Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.

Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.

Total Body Irradiation: TBI 200cGy on day -1 before transplant.

Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion

Haploidentical Stem Cell Transplant

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Claudio Brunstein

2 Year Survival

Number of Patients With Hematopoietic Engraftment

Chimerism at 6 months and 1 year not evaluated

Number of Patients With Chimerism

Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days

Data were not collected for this Outcome Measure as both participants died by the 6 month time point

Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year

Number of Patients Experiencing Transplant Related Mortality (TRM)

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).

Fludarabine: Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.

Cyclophosphamide: Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.

Total Body Irradiation: TBI 200cGy (centigray) on day -1 before transplant.

Haploidentical stem cell transplant: Non-T-cell depleted bone marrow infusion

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Anemia

Anemia, Aplastic

Hemoglobinuria

Hemoglobinuria, Paroxysmal

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Proteinuria

Urination Disorders

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Urological Manifestations

Hemolysis

Anemia, Hemolytic

Aplastic Anemia

Paroxysmal Nocturnal Hemoglobinuria

Anti-Infective Agents

Etoposide

Cytarabine

Melphalan

Etoposide phosphate

Busulfan

Cladribine

Acute Leukemias, Myelodysplastic syndromes

Chronic Leukemias, Bone Marrow Failure States, Lymphomas, Hodgkin's Disease

Acute Leukemia, Myelodysplastic syndromes, Chronic Leukemias, Bone Marrow Failure states

For patients with Multiple Myeloma, or prior autologous transplantation, or age in excess of 55

For patients undergoing a second allogeneic transplant

Allogeneic transplantation with matched unrelated donors

Allogeneic transplantation

Jeffrey W. Andrey, MD

The purpose of this study is to provide an opportunity for patients with malignancies or bone marrow failure states who lack a suitable sibling donor to undergo allogeneic hematopoietic progenitor cell transplantation using cells from unrelated individuals or cord blood registries.

Unrelated Donor Stem Cell Transplantation

Allogeneic Hematopoietic Progenitor Cell Transplantation From Unrelated Donors

Percent of donor and host cells in peripheral blood and bone marrow will be measured by short tandem repeat (STR) testing and/or standard cytogenetic testing.

Scripps Health

Skin and Connective Tissue Diseases

Carcinoma

Adenocarcinoma

Sarcoma

Sarcoma, Ewing

Rhabdomyosarcoma

Neoplasms, Connective and Soft Tissue

Myosarcoma

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Two infusions of Natural Killer (NK) cells and ALT803

Two infusions of Natural Killer (NK) Cells

Dose escalation of Natural Killer (NK) Cells from two infusion of starting at Dose Level 1 (1x10\^7 cells/kg), dose Level-1 (1x10\^6 cells/kg) if 2 of 6 patients at Level 1 develop DLTs. Escalation to dose level 2 (2.5X10\^7) and Dose level 3 (5X10\^7) is dependent on DLT

Natural Killer (NK) Cells

ALT803

David Wald, MD, PhD

The purpose of this study is to find the number of natural killer (NK) cells from non-HLA matched donors that can be safely infused into patients with cancer. NK cells are a form of lymphocytes that defend against cancer cells. NK cells in cancer patients do not work well to fight cancer. In this study, the NK cells are being donated by healthy individuals without cancer who are not "matched" by human leukocyte antigen (HLA) genes to patients. After receiving these NK cells, patients may also be given a drug called ALT803. ALT803 is a protein that keeps NK cells alive, helps them grow in number and supports their cancer-fighting characteristics. HLA-unmatched NK cell infusion is investigational (experimental) because the process has not approved by the Food and Drug Administration (FDA).

Primary Objective:

To determine the maximum tolerated dose (MTD) of ex vivo expanded non-HLA matched donor NK cells in combination with ALT-803

Secondary Objectives:

* Describe safety profile / toxicity of combining ALT-803 with NK cell adoptive therapy.
* Determine antitumor activity of allogeneic NK cells with ALT-803 support.
* Determine if a lymphocyte depleting regimen is adequate for preventing early elimination of HLA-mismatched donor NK cells by host T-cells.

Study Design:

This is a phase I study with "3+3" design with three planned dose levels of NK cells and a fixed dose of ALT-803. Three patients will be enrolled sequentially to each dose level, starting with dose level 1. Patients will be segregated to either receive ALT803 as cytokine support after NK cell infusion (starting with same dose level as Level 1) or no cytokine administration. Patients in the arm receiving ALT803 will be either hematologic malignancy patients (Cohort A) or Colon/Soft tissue sarcoma patients (Cohort B). Absence of dose limiting toxicity (DLT) in the DLT assessment period of 28 days must be documented for all patients enrolled a cell dose without ALT803 before the next cohort of patients to receive cytokines at that dose level can be enrolled. Patients can also be enrolled in parallel to the next cell dose level without cytokines.

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803

Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT-803

MTD Will be determined by dose limiting toxicity (DLT). The MTD will be defined as the dose level immediately below that at which 2 of 6 subjects experience a dose limiting toxicity.

Measure of safety of natural killer (NK) cells in the absence of HLA matching

Complete Remission (CR): Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0x10\^9/L; platelet count \>100x10\^9/L.

CR with incomplete recovery (CRi): All CR criteria except residual neutropenia or thrombocytopenia.

Partial Remission (PR):Hematologic criteria of CR; decrease of bone marrow blast percentage to 5-25%; and decrease of pretreatment bone marrow blast percentage by ≥50%.

Cytogenetic CR (CRc): Reversion to normal karyotype at the time of morphologic CR.

Resistant disease (RD): Failure to achieve CR, CRi, or PR. Death in aplasia: Deaths occurring ≥7 days after initial treatment. Death from indeterminate cause: Deaths before completing therapy, or \<7 days following completion; or deaths occurring ≥7 days after therapy with no blasts in the blood Relapse: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease

* Measurable disease: at least one measurable lesion.
* Measurable lesions: those that can be measured in at least one dimension as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
* Non-measurable lesions: all other lesions, including small lesions that are not confirmed and followed by imaging techniques.
* Baseline documentation of "Target" lesions: all measurable lesions up to a maximum of five lesions per organ and 10 lesions in total. Target lesions should be selected on the basis of their size and their suitability for accurate repeated measurements.
* Non-target lesions: all other lesions should be identified as non-target lesions. Non-target lesions include measurable lesions that exceed the maximum numbers per organ or total of all involved organs as well as non-measurable lesions.

Lymphoma response of Complete remission, partial remission, relapsed disease, stable disease, progressive disease and best response based on the Journal of Clinical Oncology criteria defined by Cheson in 2014

* Complete response (CR): complete disappearance of disease at and negative serum immunofixation.
* Partial response (PR): \>50% reduction of serum monoclonal protein concentration with \>50% reduction of tumor infiltrate and resolution of symptoms attributable to WM.
* Minor response (MR): \> 25% but l\<50% reduction of serum monoclonal immunoglobulin M (IgM) determined by protein electrophoresis and no new symptoms or signs of active disease.
* Stable disease: \< 25% reduction and \<25% increase of serum monoclonal IgM without progression of adenopathy, organomegaly, cytopenias, or clinically significant symptoms caused by disease and/or signs of WM.
* Progressive disease: fails to meet criteria for response or stable disease. Progression also requires at least a 25% increase of serum monoclonal protein from the lowest value or worsening of cytopenias, lymphadenopathy, or organomegaly, or appearance of disease-related complications.

CR/CCR

* Complete resolution of skin patches, plaques and tumors (or erythroderma)
* No evidence of abnormal lymph nodes
* Absence of circulating Sézary cells
* No evidence of new tumor (CCR) plus confirmation by skin biopsy (CR) PR
* ≥50% improvement in the summation of (∆ Skin + ∆ Lymph Node + ∆ Peripheral Blood) with at least ≥30% improvement in ∆ Skin
* No worsening in Lymph Node or Sézary cells
* No evidence of new tumors (cutaneous or non-cutaneous)

Stable Disease at 90 Days (SD90)

• Fails to meet criteria for PR or CR but absence of new cutaneous or non-cutaneous disease over 90 days

Progressive Disease (PD)

* ≥ 50% increase from nadir or baseline in styrylpyridine derivative (SPD) or any node or lesion
* ≥ 50% increase from nadir in gestational trophoblastic disease (GTD) of any node previously \>1cm in shortest diameter
* Appearance of any new cutaneous or non-cutaneous lesion during or at the end of therapy.

Stringent Complete Response (sCR)

* CR as defined below plus:

  • Normal FLC ratio and Absence of clonal cells in bone marrow CR
* Negative immunofixation on the serum and urine and:

  * Disappearance of any soft tissue plasmacytomas
  * ≤5% plasma cells in bone marrow Very good partial response (VGPR)
* Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24h PR
* ≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to \<200 mg per 24h
* If the serum and urine protein are unmeasurable, ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required
* If the serum and urine protein are unmeasurable, and serum free light assay is also unmeasurable, ≥ 50% decrease in plasmacells is required SD
* Not meeting criteria for CR, VGPR, PR, or progressive disease

Complete hematologic response

• White blood cell count \<10,000/microL with no immature granulocytes and \<5 percent basophils on differential, platelet count \<450,000/microL, and spleen not palpable.

Cytogenetic responses

* Complete cytogenetic response: No Philadelphia chromosome positive cells present.
* Partial cytogenetic response: 1 to 35 percent Philadelphia chromosome positive cells present.
* Major cytogenetic response includes patients with complete and partial cytogenetic response (ie, 0 to 35 percent Philadelphia chromosome positive cells present).
* Minor-minimal cytogenetic response: 36 to 95 percent Philadelphia chromosome positive cells present.

Molecular response:

* Complete molecular response: break cluster region - Abelson family kinases (BCR-ABL) transcript nondetectable and nonquantifiable in an assay that has at least 4 to 5 log range.
* Major molecular response: An at least three log reduction in BCR-ABL transcript levels from baseline.

Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm (the sum may not be "0" if there are target nodes). Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions may be considered progression).

Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

The duration of overall response is measured from the time of NK Cell infusion until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Overall survival is measured from the date of first infusion of NK cells to the date of death from any cause; patients not known to have died at last follow up are censored on the date they were last known to be alive.

Only those patients achieving complete response (CR) or complete response with incomplete recovery (CRI). It is measured from the date of infusion of NK cells until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow up are censored on the date they were last examined.

Measurement of in vivo NK cell levels following cell product infusion will be done on peripheral blood by flow cytometry (CD3- CD56+ positive cells). This will be done on peripheral blood samples of patients. Measurement of successful donor NK cell persistence (absence of cell product rejection) will be defined as measurement of \>100 NK cell/µL

Brenda Cooper, MD

Medical Oncology Specialist

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases	NCT02145039	Acute Leukemias Burkitt's Lymph... Chronic Myeloge...	Fludarabine Cyclophosphamid... Total Body Irra... Haploidentical ...	- 74 Years	Masonic Cancer Center, University of Minnesota
Unrelated Donor Stem Cell Transplantation	NCT01364363	Severe Aplastic... Paroxysmal Noct... Acute Myelogeno... Acute Lymphobla... Myelodysplastic... Myeloproliferat... Chronic Myeloge... Hodgkin's Lymph... Non-Hodgkin's L... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Large Granulocy...	Allogeneic tran...	18 Years - 69 Years	Scripps Health
Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803	NCT02890758	Acute Myeloid L... Myelodysplastic... Acute Lymphobla... Chronic Myeloid... Chronic Lymphoc... Non Hodgkin Lym... Hodgkin Lymphom... Myeloproliferat... Plasma Cell Mye... Colon Carcinoma Adenocarcinoma ... Soft Tissue Sar... Ewing's Sarcoma Rhabdomyosarcom...	Natural Killer ... ALT803	18 Years -	Case Comprehensive Cancer Center
Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases	NCT02145039	Acute Leukemias Burkitt's Lymph... Chronic Myeloge...	Fludarabine Cyclophosphamid... Total Body Irra... Haploidentical ...	- 74 Years	Masonic Cancer Center, University of Minnesota
Unrelated Donor Stem Cell Transplantation	NCT01364363	Severe Aplastic... Paroxysmal Noct... Acute Myelogeno... Acute Lymphobla... Myelodysplastic... Myeloproliferat... Chronic Myeloge... Hodgkin's Lymph... Non-Hodgkin's L... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Large Granulocy...	Allogeneic tran...	18 Years - 69 Years	Scripps Health
Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases	NCT02145039	Acute Leukemias Burkitt's Lymph... Chronic Myeloge...	Fludarabine Cyclophosphamid... Total Body Irra... Haploidentical ...	- 74 Years	Masonic Cancer Center, University of Minnesota

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