Haploidentical Donor Hematopoietic Stem Cell Transplant in Treating Patients With Hematologic Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Thomas Jefferson University
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01871441
First received: June 4, 2013
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

This phase II trial studies how well haploidentical donor hematopoietic stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may replace the patient's immune cells and help destroy any remaining cancer cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.


Condition Intervention Phase
Malignant Neoplasm
Radiation: Total-body irradiation
Biological: Donor lymphocytes infusion (DLI)
Drug: Cyclophosphamide
Procedure: Allogeneic hematopoietic stem cell transplantation (HSCT)
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Step Approach to Haploidentical Hematopoietic Stem Cell Transplantation for Patients in Remission From HLA Partially-Matched Related Donors-Effect of Maternal Donors on Outcomes

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Defined as the time to death, relapse or disease progression. The difference in DFS between maternal and non-maternal groups will be tested using log-rank test. The survival curves for each group will be estimated using the Kaplan-Meier estimator.


Secondary Outcome Measures:
  • Rate of relapse and GVHD in maternal recipients whose only eligible donors are offspring [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The rates of relapse and GVHD in maternal recipients whose only eligible donors are offspring will be computed with corresponding exact binomial 95% confidence intervals.

  • Rate of grade III-IV GVHD in female recipients with male donors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals.

  • The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test.


Estimated Enrollment: 52
Study Start Date: May 2013
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (haploidentical allogeneic HSCT)

Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.

Radiation: Total-body irradiation
Undergo TBI
Other Name: TBI
Biological: Donor lymphocytes infusion (DLI)
Undergo DLI
Other Names:
  • Allogeneic Lymphocytes
  • ALLOLYMPH
Drug: Cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Procedure: Allogeneic hematopoietic stem cell transplantation (HSCT)
Undergo haploidentical allogeneic HSCT
Drug: Tacrolimus
Given IV
Other Names:
  • FK-506
  • fujimycin
  • Prograf
  • Advagraf
  • Protopic
Drug: Mycophenolate mofetil
Given IV
Other Names:
  • CellCept
  • Myfortic
  • MMF

Detailed Description:

PRIMARY OBJECTIVES:

I. Examine the 1 year disease free survival (DFS) rate of patients with maternal donors or sibling donors who share the maternal haplotype (maternal group) and compare them to patients receiving cells from donors who have points from other characteristics such as killer immunoglobulin-like receptor (KIR) ligand mismatching, minor histocompatibility antigen (MHag) differences, or number of human leukocyte antigen (HLA) mismatches (non-maternal group).

SECONDARY OBJECTIVES:

I. Assess the incidences of relapse and graft-versus-host disease (GVHD) in maternal recipients whose only eligible donors are offspring.

II. Assess the incidence of grades III-IV GVHD in female recipients with male donors.

III. Compare the rates of DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch.

OUTLINE:

Patients undergo total body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.

TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.

After completion of study treatment, patients are followed up at 90, 180, and 270 days, and 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Any patient with a hematologic or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
  2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
  3. Patients must have adequate organ function:

    1. LVEF (Left ventricular ejection fraction) of >50%
    2. Diffusion Capacity for Carbon Monoxide (DLCO) >50% of predicted corrected for hemoglobin
    3. Adequate liver function as defined by a serum bilirubin <1.8, Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal
    4. Creatinine clearance of > 60 ml/min
  4. Performance status > 80% (TJU Karnofsky)
  5. Hematopoietic Comorbidity Index (HCT-CI) Score < 5 Points
  6. Patients must be willing to use contraception if they have childbearing potential
  7. Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent

Exclusion Criteria:

  1. Performance status < 80 % (TJU Karnofsky)
  2. HCT-CI Score > 5 Points
  3. Combination of Performance status of < 80% (TJU Karnofsky) and an HCT-CI of 4 points or more.
  4. HIV positive
  5. Active involvement of the central nervous system with malignancy
  6. Psychiatric disorder that would preclude patients from signing an informed consent
  7. Pregnancy
  8. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
  9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an ATG level of > 2 ugm/ml
  10. Patients who cannot receive cyclophosphamide
  11. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01871441

Contacts
Contact: Dolores Grosso, DNP, CRNP 215-955-0182
Contact: Donna Zuccarello 215-955-6612

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Dolores Grosso, DNP, CRNP         
Contact: Donna Zuccarello    215-955-6612      
Principal Investigator: Dolores Grosso, DNP, CRNP         
Sub-Investigator: Neal Flomenberg, MD         
Sub-Investigator: S. Onder Alpdogan, MD         
Sub-Investigator: Matthew Carabasi, MD         
Sub-Investigator: Joanne Filicko-O'Hara, MD         
Sub-Investigator: Ubaldo Martinez-Outschoorn, MD         
Sub-Investigator: John Wagner, MD         
Sub-Investigator: Mark Weiss, MD         
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Dolores Grosso, DNP, CRNP Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01871441     History of Changes
Other Study ID Numbers: 13D.127, 2012-104
Study First Received: June 4, 2013
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Cyclophosphamide
Mycophenolate mofetil
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on August 18, 2014