Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
50

Inclusion Criteria

Myelofibrosis and CMML
Any relapse or primary refractory disease
Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
...
Myelofibrosis and CMML
Any relapse or primary refractory disease
Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
Myeloma with evidence of persistent disease after front-line therapy.
Creatinine Clearance of ≥ 60 mL/min 4) Patients must have adequate KPS and HCT-CI scores:
Patients must have a related donor who is at least a 4 antigen match at the Human Leukocyte Antigen (HLA)-A; B; C; DR loci. Patients with only a 1 out of 8 mismatch in the GVH direction will be classified in the matched related category
Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively.
Patients aged 60 to 65 years must have a KPS of ≥80% and an HCT-CI score of 4 or less
Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q),(11q),(3q),(21q),(17p),t(6;9), t(6;11), t(11;19), +8,del(12p),inv(3),t(10;11),-17, 11q 23
Normal cytogenetics but FLT3/ITD positive
Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy
Left ventricular end diastolic function (LVEF) of >50%
Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes.
Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less (Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the PI and at least 1 Co-I not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of the protocol but have histories that result in higher than guideline HCT-CI points. An examples is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities 5) Patients must be willing to use contraception if they have childbearing potential 6) Patient or patient's guardian is able to give informed consent
Patients < age 60 years must have a KPS of ≥80% and an HCT-CI score of 5 or less
Acute lymphoid leukemia in 1st or 2nd morphological remission. ALL with any morphological evidence of disease will not be eligible.
Age greater than or equal to 60
Diffusion Lung Capacity of Oxygen (DLCO) >50% of predicted corrected for hemoglobin
Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease.
Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse. Patients in this category require specific approval of the PI and the TJU BMT attending physician group for entrance.
Any hematological malignancy or dyscrasia not cited above which is thought to be high-risk with increased chance of post HSCT relapse.
Essential Thrombocytopenia or Polycythemia Vera with current or past evidence of evolution to acute leukemia
Any single autosomal monosomy
Adequate liver function as defined by a serum bilirubin <1.8, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
Secondary AML (prior therapy or hematologic malignancy)

Exclusion Criteria

Active involvement of the central nervous system with malignancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
HIV positive
...
Active involvement of the central nervous system with malignancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
HIV positive
Pregnancy
Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Patients who have received alemtuzumab or ATG within 8 weeks of the transplant admission.

Summary

Conditions
  • Chronic Myelomonocytic Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Accelerated Phase Chronic Myelogenous Leukemia
  • Refractory Anemia With Excess Blasts in Transformation
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Grade 3 Follicular Lymphoma
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Refractory Hairy Cell Leukemia
  • Small Intestine Lymphoma
  • Essential Thrombocythemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Peripheral T Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Childhood Large Cell Lymphoma
  • Refractory Anemia With Excess Blasts
  • Recurrent Mantle Cell Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Refractory Multiple Myeloma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Childhood Myelodysplastic Syndromes
  • Chronic Phase Chronic Myelogenous Leukemia
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T Cell Lymphoma
  • Childhood Diffuse Large Cell Lymphoma
  • Intraocular Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Relapsing Chronic Myelogenous Leukemia
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Juvenile Myelomonocytic Leukemia
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Post Transplant Lymphoproliferative Disorder
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Waldenstrom Macroglobulinemia
  • Nodal Marginal Zone B-cell Lymphoma
  • Testicular Lymphoma
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Burkitt Lymphoma
  • Polycythemia Vera
  • Refractory Cytopenia With Multilineage Dysplasia
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Hepatosplenic T Cell Lymphoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Secondary Acute Myeloid Leukemia
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Childhood Immunoblastic Large Cell Lymphoma
  • Childhood Nasal Type Extranodal NK/T-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Childhood Chronic Myelogenous Leukemia
  • Primary Myelofibrosis
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVE: 1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it ...

PRIMARY OBJECTIVE: 1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it with that of the initial 2 Step RIC regimen. SECONDARY OBJECTIVES: To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this treatment protocol. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial. OUTLINE: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -15 to -12, thiotepa IV over 2 hours on days -15 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -10. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV twice daily (BID) on days -1 to 28. After completion of study treatment, patients are followed up periodically.

Inclusion Criteria

Myelofibrosis and CMML
Any relapse or primary refractory disease
Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
...
Myelofibrosis and CMML
Any relapse or primary refractory disease
Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
Myeloma with evidence of persistent disease after front-line therapy.
Creatinine Clearance of ≥ 60 mL/min 4) Patients must have adequate KPS and HCT-CI scores:
Patients must have a related donor who is at least a 4 antigen match at the Human Leukocyte Antigen (HLA)-A; B; C; DR loci. Patients with only a 1 out of 8 mismatch in the GVH direction will be classified in the matched related category
Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively.
Patients aged 60 to 65 years must have a KPS of ≥80% and an HCT-CI score of 4 or less
Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q),(11q),(3q),(21q),(17p),t(6;9), t(6;11), t(11;19), +8,del(12p),inv(3),t(10;11),-17, 11q 23
Normal cytogenetics but FLT3/ITD positive
Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy
Left ventricular end diastolic function (LVEF) of >50%
Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes.
Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less (Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the PI and at least 1 Co-I not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of the protocol but have histories that result in higher than guideline HCT-CI points. An examples is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities 5) Patients must be willing to use contraception if they have childbearing potential 6) Patient or patient's guardian is able to give informed consent
Patients < age 60 years must have a KPS of ≥80% and an HCT-CI score of 5 or less
Acute lymphoid leukemia in 1st or 2nd morphological remission. ALL with any morphological evidence of disease will not be eligible.
Age greater than or equal to 60
Diffusion Lung Capacity of Oxygen (DLCO) >50% of predicted corrected for hemoglobin
Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease.
Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse. Patients in this category require specific approval of the PI and the TJU BMT attending physician group for entrance.
Any hematological malignancy or dyscrasia not cited above which is thought to be high-risk with increased chance of post HSCT relapse.
Essential Thrombocytopenia or Polycythemia Vera with current or past evidence of evolution to acute leukemia
Any single autosomal monosomy
Adequate liver function as defined by a serum bilirubin <1.8, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
Secondary AML (prior therapy or hematologic malignancy)

Exclusion Criteria

Active involvement of the central nervous system with malignancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
HIV positive
...
Active involvement of the central nervous system with malignancy
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
HIV positive
Pregnancy
Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Patients who have received alemtuzumab or ATG within 8 weeks of the transplant admission.

Locations

Philadelphia, Pennsylvania, 19107
Philadelphia, Pennsylvania, 19107

Tracking Information

NCT #
NCT01760655
Collaborators
Not Provided
Investigators
  • Principal Investigator: Dolores Grosso, RN, CRNP, DNP Thomas Jefferson University Principal Investigator: Neal Flomenberg, MD Thomas Jefferson University
  • Dolores Grosso, RN, CRNP, DNP Thomas Jefferson University Principal Investigator: Neal Flomenberg, MD Thomas Jefferson University