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

Roswell Park Comprehensive Cancer Center

Status: Completed

Conditions: Multiple Myeloma and Plasma Cell Neoplasm; Lymphoma; Leukemia; Myelodysplastic Syndromes

Treatments: Biological: donor lymphocytes

Study type: Interventional

Funder types: Other

Identifiers

NCT00534118

RPCI-I-00703

CDR0000564827

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: Under 76 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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39 participants in 1 patient group

Infusion

Experimental group

Description:

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

Treatment:

Biological: donor lymphocytes