Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases

December 12, 2019 updated by: Masonic Cancer Center, University of Minnesota

Reduced Intensity Conditioning (RIC) and Transplantation of HLA(Human Leukocyte Antigen)-Haploidentical Related Bone Marrow (Haplo-BM) For Patients With Hematologic Diseases

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Masonic Cancer Center

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.

Eligibility Criteria

Ages Eligible for Study

No older than 74 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must be <75 years old with no 7/8 or 8/8 HLA-matched sibling donor
  • One or more potential related mismatched donors (e.g. biologic parent (s) or siblings (full or half) or children). Low resolution using DNA based typing at HLA-A, -B and -DRB1 for potential haploidentical donors is required.

  • All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.

    • Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk.
    • Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk.
    • Acute Leukemias in 2nd or subsequent CR
    • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR
    • Burkitt's lymphoma in CR2 or subsequent CR
    • Natural killer cell malignancies after response to initial therapy
    • Chronic myelogenous leukemia: all types except refractory blast crisis.
    • Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant.
    • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of achieving a partial or complete remission.
    • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
    • Refractory leukemia or MDS These patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody.
    • Bone marrow failure syndromes, except for Fanconi Anemia
    • Myeloproliferative syndromes

  • Adequate organ function is defined as:

    • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%. For children that are not able to cooperate with multigated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician's note
    • Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) > 30% predicted, and absence of O2 requirements. For children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted. If nether test can be obtained it should be clearly stated in the physician's note.
    • Liver: Transaminases < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
    • Renal: serum creatinine < 2.0 mg/dl (adults) or glomerular filtration rate (GFR) >40 mL/min/1.73m2 (peds). Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2.
    • Adequate performance status is defined as Karnofsky score ≥ 60% (> 16 years of age) or Lansky score ≥ 50 (pediatrics)
  • If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before bone marrow transplant (BMT) and infection controlled and be cleared by Infectious Disease.
  • Second BMT: Must be > 3 months after prior myeloablative transplant.
  • Patients must be ineligible for autologous transplantation due to prior autologous transplant, an inadequate autologous stem cell harvest, inability to withstand a myeloablative preparative regimen, or clinically aggressive/high risk disease.
  • Patients are eligible for transplantation if there is no evidence of progressive disease by imaging modalities or biopsy. Persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
  • Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).
  • Voluntary written consent (adult or parental/guardian)

Exclusion Criteria:

  • Available and clinically suitable 5-6/6 HLA-A, B, DRB1 matched sibling donor
  • Pregnant or breastfeeding
  • Evidence of HIV infection or known HIV positive serology
  • Current active serious infection
  • Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible, patients with acute leukemia in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
  • Chronic myeloid leukemia (CML) in refractory blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
  • active central nervous system malignancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Haploidentical stem cell transplant
This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).
Drug: Fludarabine
Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.
Other Names:
  • Fludara
Drug: Cyclophosphamide
Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.
Radiation: Total Body Irradiation
TBI 200cGy on day -1 before transplant.
Other Names:
  • TBI
Biological: Haploidentical stem cell transplant
Non-T-cell depleted bone marrow infusion
Other Names:
  • HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2 Year Survival
Time Frame: 2 years
Percentage of patients that survive 2 years post-transplant
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Hematopoietic Engraftment
Time Frame: 42 days
Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements.
42 days
Number of Patients With Chimerism
Time Frame: 100 days
Number of patients with chimerism at day 100, 6 months and 1 year
100 days
Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days
Time Frame: 100 days
100 days
Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year
Time Frame: 1 year
1 year
Number of Patients Experiencing Transplant Related Mortality (TRM)
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

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 Major Dates

Study Start (Actual)

October 1, 2014

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

May 20, 2014

First Submitted That Met QC Criteria

May 20, 2014

First Posted (Estimate)

May 22, 2014

Study Record Updates

Last Update Posted (Actual)

December 26, 2019

Last Update Submitted That Met QC Criteria

December 12, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013OC116
  • MT2013-33C (Other Identifier: University of Minnesota Blood and Marrow Transplant Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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