Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

April 10, 2017 updated by: Fred Hutchinson Cancer Center

Nonmyeloablative Hematopoietic Stem Cell Transplantation for Patients With High-Risk Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression Before and After Transplantation

This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. To determine if engraftment can be achieved safely in patients with high-risk hematologic malignancies who undergo non-myeloablative bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-haploidentical donors.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus orally (PO), once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

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
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic myeloid leukemia (CML) in accelerated phase (AP)
  • Acute myeloid leukemia (AML) with high-risk cytogenetics [del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6:9), t(9;22), complex karyotypes (>= 3 abnormalities)] in complete remission (CR)1
  • AML >= CR2; patients should have < 5% marrow blasts at the time of transplant
  • High-risk ALL defined as: CR1 with high-risk cytogenetics; t(9;22), t(4;11), or hypodiploid (< 45 chromosomes) for pediatric patients; t(9;22), t(8;14), t(4;11), t(1;19) for adult patients; > 4 wk to achieve CR1; >= CR2 (patients should have < 5% marrow blasts at the time of transplant)
  • Myelodysplastic syndromes (MDS) (>int-1 per IPSS) after >= 1 prior cycle of induction chemotherapy; should have < 5% marrow blasts at the time of transplant
  • Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
  • Chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) or Hodgkin's Disease (HD) who are ineligible for autologous HSCT or who have resistant/refractory disease and who may benefit from tandem autologous nonmyeloablative allogeneic transplant
  • Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active graft-versus-host disease (GvHD) requiring immunosuppressive therapy
  • DONOR: Related donors who are identical for one HLA haplotype and mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches

Exclusion Criteria:

  • Cross-match positive with donor
  • Patients with suitably matched related or unrelated donors
  • Patients with conventional transplant options (a conventional transplant should be the priority for eligible patients =< 50 yr of age who have a related donor mismatched for a single HLA-A, -B or DRB1 antigen)
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
  • Presence of active, serious infection (e.g., mucormycosis, uncontrolled aspergillosis, tuberculosis)
  • Karnofsky Performance Status < 60 for adult patients
  • Lansky-Play Performance Score < 60 for pediatric patients
  • Left ventricular ejection fraction < 35%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 35% and/or receiving supplemental continuous oxygen
  • Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL or symptomatic biliary disease
  • Human immunodeficiency virus (HIV)-positive patients
  • Women of childbearing potential who are pregnant (beta-HCG+) or breast feeding
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction
  • DONOR: Cross-match positive with recipient

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: Treatment (nonmyeloablative HSCT)

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus PO, once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Genetic: polymerase chain reaction
Correlative studies
Other Names:
  • PCR
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Drug: tacrolimus
Given IV or orally
Other Names:
  • Prograf
  • FK 506
Genetic: fluorescence in situ hybridization
Correlative studies
Other Names:
  • fluorescence in situ hybridization (FISH)
Drug: mycophenolate mofetil
Given orally
Other Names:
  • Cellcept
  • MMF
Genetic: polymorphism analysis
Correlative studies
Genetic: gene expression analysis
Correlative studies
Radiation: total-body irradiation
Undergo total-body irradiation
Other Names:
  • TBI
Procedure: allogeneic bone marrow transplantation
Undergo haploidentical hematopoietic bone marrow transplantation
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo haploidentical hematopoietic bone marrow transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Donor Engraftment (Chimerism)
Time Frame: At day +84 after transplantation
Defined by the detection of at least 50% donor derived T-cells (CD3+), as a proportion of the total T-cell population
At day +84 after transplantation
Incidence of Grades III-IV Acute GVHD
Time Frame: At any time within 200 days after transplantation
Grade III GVHD represents moderate severity. Grade IV GVHD represents extreme severity
At any time within 200 days after transplantation
Non-relapse-related Mortality
Time Frame: Up to 200 days after transplantation
Number of deaths without progression or recurrence of malignant disease
Up to 200 days after transplantation

Collaborators and Investigators

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

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Paul O'Donnell, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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)

January 1, 2002

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

November 12, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

May 17, 2017

Last Update Submitted That Met QC Criteria

April 10, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1667.00
  • NCI-2010-00166 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Individual patient data is protected by HIPAA at each participant organization.

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

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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