A new approach to stem cell transplantation for blood cancers

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

This study is testing a new two-step method for stem cell transplants in patients with serious blood cancers to see if it helps them live longer and have fewer side effects.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Thomas Jefferson University (other)
• Drugs / interventions: Alemtuzumab, chemotherapy, cyclophosphamide
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT03032783 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of a two-step approach to allogeneic hematopoietic stem cell transplantation in patients with high-risk hematologic malignancies. The study involves administering total-body irradiation and chemotherapy prior to the transplant to enhance the graft-versus-tumor (GVT) effects while minimizing toxicity. The primary objective is to evaluate the two-year overall survival probability, while secondary objectives include assessing relapse rates, treatment-related toxicity, and immune recovery post-transplant. The trial aims to improve patient outcomes by optimizing the transplant process.

Who should consider this trial

Good fit: Ideal candidates include patients with high-risk hematologic malignancies who are either untreated or have stable residual disease and are expected to benefit from allogeneic stem cell transplantation.

Not a fit: Patients with low-risk hematologic malignancies or those who are not candidates for stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and reduce relapse in patients with high-risk blood cancers.

How similar studies have performed: Other studies have shown promising results with similar approaches to stem cell transplantation, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

This treatment is for patients with high risk hematologic malignancies. High risk is defined as:

* 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

Exclusion Criteria:

* 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.

Where this trial is running

Philadelphia, Pennsylvania

• Sidney Kimmel Cancer Center at Thomas Jefferson University — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Usama Gergis, MD — Sidney Kimmel Cancer Center at Thomas Jefferson University
• Study coordinator: Usama Gergis, MD

Conditions: Hematopoietic and Lymphoid Cell Neoplasm