Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant

August 21, 2020 updated by: Roswell Park Cancer Institute

Cellular Infusions in Patients With Recurrent or Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplant

RATIONALE: Giving an infusion of donor lymphocytes may be able to kill cancer cells in patients with hematologic cancer that has come back after a donor stem cell transplant.

PURPOSE: This clinical trial is studying how well donor lymphocyte infusion works in treating patients with recurrent or persistent hematologic cancer after donor stem cell transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine if the complete response rate exceeds 10% in patients with recurrent or persistent hematologic malignancies treated with donor lymphocyte infusion.

Secondary

  • Estimate the complete response rate in these patients.
  • Assess the toxicity of donor lymphocyte infusion in these patients.

OUTLINE: Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease.

Study Type

Interventional

Enrollment (Actual)

39

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
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute

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 76 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Has undergone allogeneic stem cell transplantation (ASCT) for hematologic malignancy at least 30 days ago

    • No failure to engraft following transplant

    • No active acute or chronic graft-versus-host disease (GVHD)

      • Minimal GVHD allowed

  • Persistent or relapsed disease after ASCT, including 1 of the following:

    • Chronic myelogenous leukemia (CML), meeting any of the following criteria:

      • Molecular relapse (may be treated with imatinib mesylate after transplant), as defined by any of the following:

        • ASCT was non-T-cell depleted, a negative bcr/abl was documented by PCR post-transplant, and bcr/abl is now detectable by 2 consecutive PCR determinations > 30 days apart
        • ASCT was non-T-cell depleted and bcr/abl is detectable by PCR at any time after day 180 post-transplant
      • Cytogenetic relapse after 3-6 months of imatinib mesylate

      • Relapsed chronic phase, accelerated phase, or blastic phase CML after 3-6 months of imatinib mesylate

        • Must currently be in chronic phase or accelerated phase CML only
        • Patients with blastic phase CML must attain a second chronic phase

    • Acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes, meeting any of the following criteria:

      • Molecular relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific molecular abnormality detectable by PCR
      • Cytogenetic relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific chromosome abnormality detectable by standard cytogenetics at any time after day 60 post-transplant

      • Hematologic relapse, as evidenced by > 20% blasts in bone marrow or soft tissue recurrence

        • Must be treated with chemotherapy after transplant, but before study donor lymphocyte infusion (DLI)

    • Multiple myeloma

      • Relapsed disease or recurrence of M-protein after thalidomide or other salvage treatment

        • Prior post-transplant documentation of disappearance of M-protein by immunofixation
      • Residual or progressive disease
      • Rising M-protein level at any time post-transplant (measured at 3-month intervals)
      • Original M-protein detectable at 6 months post-transplant
      • Immune protein electrophoresis (IPEP) is required to show that M-component is the same on day 60 post-transplant as pre-transplant
      • Residual (> 5%) plasma cells in bone marrow

    • Relapsed non-Hodgkin lymphoma or Hodgkin lymphoma

      • Relapse or progression of disease must be evidenced within 3 months prior to donor lymphocyte infusion by physical exam, radiographic studies, or molecular studies

        • Tumor should be re-biopsied to determine histology
      • If Epstein-Barr virus (EBV) lymphoma is suspected, peripheral blood must be assayed for EBV genome (i.e., EBV DNA testing by PCR) within the past 30 days

    • EBV infection with associated pancytopenia

      • Persistent or refractory pancytopenia with EBV genome detected by PCR in the peripheral blood

        • Refractory pancytopenia is defined as pancytopenia that is poorly responsive to growth factors and/or transfusions

    • EBV lymphoproliferative disorder

      • Clonal lymphadenopathy that is refractory to standard therapy with acyclovir and immunoglobulin (DLI may be given with rituximab)

  • Not a candidate for repeat ASCT

    • Chimerism status is not required for determining eligibility for DLI
  • Patients eligible for allogeneic ASCT, but for whom DLI is offered as the first option, should have full donor chimerism at relapse or after therapy for relapsed disease
  • Patients with relapsed underlying disease after transplant who achieved remission after chemotherapy are allowed

  • No CNS recurrence that is not cleared by standard chemotherapy

    • CNS remission status must be maintained for 2 weeks

  • Original hematopoietic progenitor stem cell donor must be available for cell donation

    • No syngeneic donors

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy ≥ 8 weeks
  • Creatinine < 3 mg/dL
  • ABO/Rh and CMV IgG/IgM status known
  • No HIV1 and HIV2 antibody
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months (males) or 6 months (females) after completion of study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

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: Infusion
Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease
Biological: donor lymphocytes
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission Rate
Time Frame: 100 days post DLI
continued or induced complete remission after DLI
100 days post DLI
Duration of Complete Response in Months (Maximum 12)
Time Frame: 1 year post DLI
For participants who achieve a complete remission after DLI, the duration of time until 1) relapse or 2) death in remission or 3) subsequent DLI or 4) last followup (at 1 year after DLI)
1 year post DLI

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Graft-versus-host Disease
Time Frame: 100 days post DLI
development of grade III-IV acute graft-versus-host disease (GVHD) per Glucksberg criteria
100 days post DLI

Collaborators and Investigators

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

Sponsor

Roswell Park Cancer Institute

Investigators

  • Principal Investigator: Philip L. McCarthy, MD, Roswell Park Cancer Institute

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, 2003

Primary Completion (Actual)

July 26, 2018

Study Completion (Actual)

July 26, 2018

Study Registration Dates

First Submitted

September 20, 2007

First Submitted That Met QC Criteria

September 20, 2007

First Posted (Estimate)

September 24, 2007

Study Record Updates

Last Update Posted (Actual)

August 26, 2020

Last Update Submitted That Met QC Criteria

August 21, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000564827
  • RPCI-I-00703

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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