COMPLETED

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies-Increasing GVT Effects Without Increasing Toxicity

Conditions

Hematopoietic and Lymphoid Cell Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies the how well donor stem cell transplant works in treating patients with high risk hematologic malignancies. Giving total-body irradiation and chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Official Title

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies-Increasing GVT Effects Without Increasing Toxicity

Quick Facts

Study Start:2017-01-31

Study Completion:2025-12-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:COMPLETED

Study ID

NCT03032783

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Any patient with a hematologic malignancy in which allogeneic HSCT is pursued with the expectation of cure. Patients may have post-treatment residual disease, but the disease should be stable or minimally progressive and must be responsive to chemotherapy. * Any patient with an untreated hematologic malignancy in which allogeneic HSCT is thought to be the sole or the best option for cure and in Patients without morphologic evidence of disease but with high risk features which would predict for relapsed despite remission at HSCT such as adverse cytogenetics, 3rd or greater CR, or failure to recover peripheral blood counts to normal ranges. While these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive. * Patients with uncommon diagnoses in which allogeneic HSCT is thought to be beneficial but are no comparable to the majority of patients on this protocol will not be counted in the statistical aims of the study and will be reported descriptively. The PI and at least one Co-I must document this exception in the study binder and the rationale for descriptive report. An example of a patient who may meet this criteria is someone with a malignancy that is an overlap of two different diagnoses or one whose malignancy is difficult to categorize. While this circumstance is expected to be rare, it will prevent patients with rare diagnoses to be treated off study and it will help maintain homogeneity of the study population. * Patients must have one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci (except as described below) * Patients must have adequate organ function: * Left Ventricular Ejection Fraction (LVEF) of ≥50% * DLCO (adjusted for hemoglobin) ≥50% of predicted and FEV-1 ≥50% * Adequate liver function as defined by a serum bilirubin ≤1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) * Creatinine clearance of ≥ 60ml/min * Karnofsky Performance Status (KPS) of ≥80% on the modified KPS tool (see Appendix) * Patients must be willing to use contraception if they have childbearing potential * Able to give informed consent * Age ≥ 18 years of age	* Modified KPS of \<80% * \> 5 Comorbidity Points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI) (See Appendix) (Patients with greater than 5 points will be allowed 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 this protocol but have histories that result in higher than HCT-CI 5 points. An example 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. * Human Immunodeficiency Virus (HIV) positive * Active involvement of the central nervous system with malignancy * Psychiatric disorder that would preclude patients from signing an informed consent * Pregnancy, or unwillingness to use contraception if they have childbearing potential * Patients with life expectancy of ≤ 6 months for reasons other than their underlying hematologic/oncologic disorder * Alemtuzumab treatment within 8 weeks of HSCT admission * ATG within 8 weeks of HSCT administration * Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan.

Inclusion Criteria

Exclusion Criteria

* Any patient with a hematologic malignancy in which allogeneic HSCT is pursued with the expectation of cure. Patients may have post-treatment residual disease, but the disease should be stable or minimally progressive and must be responsive to chemotherapy.
* Any patient with an untreated hematologic malignancy in which allogeneic HSCT is thought to be the sole or the best option for cure and in Patients without morphologic evidence of disease but with high risk features which would predict for relapsed despite remission at HSCT such as adverse cytogenetics, 3rd or greater CR, or failure to recover peripheral blood counts to normal ranges. While these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive.
* Patients with uncommon diagnoses in which allogeneic HSCT is thought to be beneficial but are no comparable to the majority of patients on this protocol will not be counted in the statistical aims of the study and will be reported descriptively. The PI and at least one Co-I must document this exception in the study binder and the rationale for descriptive report. An example of a patient who may meet this criteria is someone with a malignancy that is an overlap of two different diagnoses or one whose malignancy is difficult to categorize. While this circumstance is expected to be rare, it will prevent patients with rare diagnoses to be treated off study and it will help maintain homogeneity of the study population.
* Patients must have one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci (except as described below)
* Patients must have adequate organ function:
* Left Ventricular Ejection Fraction (LVEF) of ≥50%
* DLCO (adjusted for hemoglobin) ≥50% of predicted and FEV-1 ≥50%
* Adequate liver function as defined by a serum bilirubin ≤1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN)
* Creatinine clearance of ≥ 60ml/min
* Karnofsky Performance Status (KPS) of ≥80% on the modified KPS tool (see Appendix)
* Patients must be willing to use contraception if they have childbearing potential
* Able to give informed consent
* Age ≥ 18 years of age

* Modified KPS of \<80%
* \> 5 Comorbidity Points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI) (See Appendix) (Patients with greater than 5 points will be allowed 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 this protocol but have histories that result in higher than HCT-CI 5 points. An example 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.
* Human Immunodeficiency Virus (HIV) positive
* Active involvement of the central nervous system with malignancy
* Psychiatric disorder that would preclude patients from signing an informed consent
* Pregnancy, or unwillingness to use contraception if they have childbearing potential
* Patients with life expectancy of ≤ 6 months for reasons other than their underlying hematologic/oncologic disorder
* Alemtuzumab treatment within 8 weeks of HSCT admission
* ATG within 8 weeks of HSCT administration
* Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan.

Contacts and Locations

Principal Investigator

Usama Gergis, MD

PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Study Locations (Sites)

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Philadephia, Pennsylvania, 19107

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Usama Gergis, MD, PRINCIPAL_INVESTIGATOR, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-01-31

Study Completion Date2025-12-02

Study Record Updates

Study Start Date2017-01-31

Study Completion Date2025-12-02

Terms related to this study

Additional Relevant MeSH Terms

Hematopoietic and Lymphoid Cell Neoplasm