Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Diseases

August 7, 2018 updated by: Wake Forest University Health Sciences

Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, mycophenolate mofetil, and antithymocyte globulin before and after transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer or abnormal cells as not belonging in the patient's body and destroy them (graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with hematologic cancer or other diseases.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases.

Secondary

  • Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen.
  • Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • Determine other toxicities of this regimen in these patients.
  • Determine the overall survival and disease-free survival of patients treated with this regimen.
  • Determine the impact of iron status on overall and disease-free survival.
  • Determine the influence of quality of life (at time of transplantation) on overall survival.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.
  • Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.
  • Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 .

Quality of life is assessed at baseline.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

66

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
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive 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 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed hematological disease, including any of the following:

    • Chronic lymphocytic leukemia

      • Absolute lymphocytosis > 5,000/µL
      • Morphologically mature lymphocytes with < 55% prolymphocytes
      • Lymphocyte phenotype with expression of CD19 and CD5
      • Absence of CD23 expression allowed provided disease is morphologically distinguished from mantle cell lymphoma

    • Prolymphocytic leukemia

      • Absolute lymphocytosis > 5,000/µL
      • Morphologically mature lymphocytes with > 55% prolymphocytes

    • Non-Hodgkin's or Hodgkin's lymphoma

      • Any WHO classification histologic subtype
      • Diagnosis by core biopsy allowed provided there is adequate tissue for diagnosis and immunophenotyping
      • Diagnosis by bone marrow biopsy not acceptable for follicular lymphomas

    • Multiple myeloma

      • Has received ≥ 1 prior treatment regimen
      • Has a partial response or greater by the Blade Criteria
      • Patients who achieved complete remission are eligible

    • Acute myeloid leukemia

      • Documented control (i.e., < 10% bone marrow blasts and no circulating blasts)

    • Myelodysplastic syndromes

      • Documented disease as defined by WHO or French-American-British Cooperative group criteria
      • Chronic myelogenous leukemia
    • Patients with atypical chronic myelogenous leukemia (i.e., absent Philadelphia chromosome) are eligible

    • Polycythemia vera

      • Documented disease as defined by WHO criteria (i.e., A1 + A2, and any other category A, OR A1 + A2, and any 2 category B):

        • A1: Total red blood cell mass > 25% above mean normal predicted value OR hemoglobin > 18.5 g/dL in males, 16.5 g/dL in females (hematocrit ≥ 60% in males or ≥ 56% in females)
        • A2: No cause of secondary erythrocytosis (absence of familial erythrocytosis, no elevation of epoetin alfa [EPO] due to hypoxia, high oxygen affinity hemoglobin, truncated EPO receptor, or inappropriate ectopic EPO production)
        • A3: Splenomegaly
        • A4: Clonal genetic abnormality other than the Philadelphia chromosome
        • A5: Endogenous erythroid colony formation in vitro
        • B: Platelet count > 400,000/mm³, WBC > 12,000/mm³, bone marrow biopsy with prominent erythroid and megakaryocytic proliferation, and low serum EPO

    • Chronic idiopathic myelofibrosis

      • Documented disease as defined by WHO criteria
      • Must have a HLA-identical donor, a matched unrelated donor, or a HLA 9/10 related donor meeting the following criteria:

      • HLA-identical sibling (6/6)

        • Serologic typing for class I (A, B)
        • Molecular typing for class II (DRB1)

      • 9/10 matched related donor

        • High-resolution molecular typing at HLA-A, B, C, DRB1, and DQB1
        • Only a single mismatch at one class I or II allele allowed

      • 10/10 matched unrelated donor

        • Molecular identity at HLA-A, B, C, DRB1, and DQB1 by high-resolution typing
        • Syngeneic donors are not eligible
  • Creatinine clearance ≥ 40 mL/min
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • DLCO ≥ 40% with no symptomatic pulmonary disease
  • LVEF ≥ 30% by cardiac MRI or echocardiogram with no symptomatic cardiac disease
  • Fertile patients willing to use effective contraception

Exclusion Criteria:

  • Uncontrolled diabetes mellitus
  • Active serious infection
  • Known hypersensitivity to E. coli-derived products
  • Known HIV positivity

  • History of another malignancy*, meeting the following criteria:

    • Non-skin malignancy or melanoma within the past 5 years
    • Concomitant malignancy that has not been curatively treated
    • NOTE: *However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment and are deemed at low risk of < 30% for recurrence by their treating physicians is considered
  • Pregnant or nursing

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Treatment-related Mortality Within the First 6 Months After Transplantation
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete Response
Time Frame: monthly
monthly
Overall Survival
Time Frame: monthly
monthly
Disease-free Survival
Time Frame: monthly
monthly
Graft-versus-host Disease
Time Frame: monthly
monthly
Iron Status at the Time of Transplantation
Time Frame: baseline
baseline
Quality of Life at the Time of Transplantation
Time Frame: baseline
baseline
Treatment-related Mortality at 100 Days After Transplantation
Time Frame: 100 days
100 days

Collaborators and Investigators

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

Sponsor

Wake Forest University Health Sciences

Investigators

  • Study Chair: David Hurd, MD, Wake Forest University Health Sciences

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

February 1, 2007

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

March 27, 2007

First Submitted That Met QC Criteria

March 27, 2007

First Posted (Estimate)

March 28, 2007

Study Record Updates

Last Update Posted (Actual)

September 10, 2018

Last Update Submitted That Met QC Criteria

August 7, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00001366 (Other Identifier: WFUHS IRB)
  • CCCWFU-29506 (Other Identifier: CCCWFU)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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.

Clinical Trials on Lymphoma

Clinical Trials on allogeneic bone marrow transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Vietnam

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe