Donor Stem Cell Transplant in Treating Patients with High Risk Hematologic Malignancies

Status: Active

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.

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 which prior treatment is unlikely to meaningfully address the disease * Patients without morphologic evidence of disease but with high risk features which would predict for relapsed despite remission at HSCT such as adverse cytogenetics, third (3rd) or greater complete response (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 must have one related donor who is human leukocyte antigen (HLA) mismatched in the GVHD direction at two or more HLA loci
  • Left ventricular ejection fraction (LVEF) of >= 50%
  • Carbon monoxide diffusing capability test (DLCO) (adjusted for hemoglobin) >= 50% of predicted and forced expiratory volume in 1 second (FEV-1) >= 50%
  • Serum bilirubin =< 1.8
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Creatinine clearance of >= 60 ml/min
  • Karnofsky performance status (KPS) of >= 80% on the modified KPS tool
  • Patients must be willing to use contraception if they have childbearing potential
  • Able to give informed consent

Exclusion Criteria

  • Modified KPS of < 80%
  • > 5 comorbidity points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI) (patients with greater than 5 points will be allowed for trial with approval of the principal investigator [PI] and at least 1 cooperative investigator [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
  • Anti-thymocyte globulin (ATG) within 8 weeks of HSCT admission
  • Patients with active inflammatory processes including T max > 101 or active tissue inflammation are excluded up to and including the day of admission
  • Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Locations & Contacts

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: Dolores Grosso
Phone: 215-955-8874

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess 2 year probability of overall survival (OS) in high risk patients undergoing a myeloablative 2 step hematopoietic stem cell transplantation (HSCT) utilizing strategies to decrease relapse.

SECONDARY OBJECTIVES:

I. To assess relapse incidence at 2 years post-HSCT of patients undergoing treatment on this protocol.

II. To assess regimen related toxicity and graft versus host disease (GVHD) incidence at 2 years post-HSCT and severity in patients undergoing treatment on this protocol.

III. To assess the consistency and pace of engraftment.

IV. To assess the pace of T cell and B cell immune recovery.

OUTLINE:

Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -8 and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide intravenously (IV) on days -3 and -2, tacrolimus IV beginning on day -1 and then orally (PO) at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV BID on days -1 to 28. Patients undergo HSCT on day 0.

After completion of study treatment, patients are follow up for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Thomas Jefferson University Hospital

Principal Investigator
Dolores Grosso

Trial IDs

Primary ID 16D.606
Secondary IDs NCI-2017-00094
Clinicaltrials.gov ID NCT03032783