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

• ClinicalTrials.gov Identifier: NCT00534118
• Recruitment Status: Completed
• First Posted: September 24, 2007
• Results First Posted: August 26, 2020
• Last Update Posted: August 26, 2020
• Sponsor: Roswell Park Cancer Institute
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Tracking Information

• First Submitted Date: September 20, 2007
• First Posted Date: September 24, 2007
• Results First Submitted Date: July 29, 2020
• Results First Posted Date: August 26, 2020
• Last Update Posted Date: August 26, 2020
• Actual Study Start Date: October 1, 2003
• Actual Primary Completion Date: July 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 21, 2020)

• Complete Remission Rate [ Time Frame: 100 days post DLI ]
  continued or induced complete remission after 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)

Original Primary Outcome Measures (submitted: September 20, 2007)

• Response rate
• Percent of complete responses
• Duration of response

Current Secondary Outcome Measures (submitted: August 21, 2020)

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

• Original Secondary Outcome Measures (submitted: September 20, 2007): Toxicity
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant
• Official Title: Cellular Infusions in Patients With Recurrent or Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplant

Brief Summary

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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes

Intervention

Biological: donor lymphocytes

Given IV

Study Arms

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

Intervention: Biological: donor lymphocytes

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 27, 2013): 39
• Original Enrollment (submitted: September 20, 2007): 50
• Actual Study Completion Date: July 26, 2018
• Actual Primary Completion Date: July 26, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 76 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00534118
• Other Study ID Numbers: CDR0000564827; RPCI-I-00703
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Roswell Park Cancer Institute
• Study Sponsor: Roswell Park Cancer Institute
• Collaborators: Not Provided

Investigators

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

• PRS Account: Roswell Park Cancer Institute
• Verification Date: August 2020