Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

NCT01341301 | Completed Phase 2 Results DMC

• 3 other identifiers: 10D.062009-41JT 1521
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.

Conditions

Hematologic Malignancy

Keywords

allogeneic stem cell transplant; TJU 2 Step; HSCT; Hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)

  To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.

  1 year after undergoing hematopoietic stem cell transplant

Secondary Outcomes (3)

• Pace of T-cell and B-cell Immune Recovery

  Assessed up to 1 year

• Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0

  Assessed up to 1 year

• Incidence and Severity of GVHD, Graded According to Standard Criteria

  Assessed up to 1 year

Study Arms (1)

Allogeneic HSCT

EXPERIMENTAL

CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28.

Radiation: Total Body Irradiation; Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Procedure: Allogeneic hematopoietic stem cell transplantation; Other: Laboratory biomarker analysis

Interventions

Total Body Irradiation RADIATION

Undergo TBI

Also known as: TBI

Allogeneic HSCT

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

Undergo DLI

Also known as: DLI

Allogeneic HSCT

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan, Endoxan, Endoxana, Enduxan

Allogeneic HSCT

Tacrolimus DRUG

Given IV or PO

Also known as: Advagraf, Prograf, Protopic

Allogeneic HSCT

Mycophenolate mofetil DRUG

Given IV or PO

Also known as: Cellcept

Allogeneic HSCT

Allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic HSCT

Allogeneic HSCT

Laboratory biomarker analysis OTHER

Correlative studies

Allogeneic HSCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR).
• Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie \<5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
• Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci.
• Patients must adequate organ function:
• Left ventricular ejection fraction (LVEF) of \>50 %
• Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) \>50 % of predicted
• Adequate liver function as defined by a serum bilirubin \<1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5 times upper limit of normal
• Creatinine clearance of \> 60 ml/min
• Karnofsky Performance Status of \> 80% on the modified KPS tool
• Patients must be willing to use contraception if they have childbearing potential.
• Able to give informed consent

You may not qualify if:

• Modified Karnofsky performance status (KPS) of \<80%
• \> 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index
• Untreated class I or II antibodies against donor HLA antigens
• 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 child bearing 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) level of \> 2 ugm/ml
• Patients with active inflammatory processes including Tmax \>101 or active tissue inflammation are excluded
• Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Whole-Body Irradiation; Cyclophosphamide; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Neal Flomenberg
• Organization: Thomas Jefferson University

neal.flomenberg@jefferson.edu

215-955-8874

Study Officials

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Dolores Grosso, DNP, CRNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: April 25, 2011
• Study Start: May 1, 2010
• Primary Completion: November 4, 2013
• Study Completion: August 7, 2014
• Last Updated: April 30, 2025
• Results First Posted: March 16, 2018

Record last verified: 2025-04

Locations

US (1)