Clinical trial NCT00534118: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
childhood chronic myelogenous leukemia
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
recurrent adult grade III lymphomatoid granulomatosis
Waldenstrom macroglobulinemia
recurrent childhood grade III lymphomatoid granulomatosis
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent childhood small noncleaved cell lymphoma
de novo myelodysplastic syndromes
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
cutaneous B-cell non-Hodgkin lymphoma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2007-09-24
Enrollment: 39
Sex: ALL
Maximum age (years): 76
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete Remission Rate
timeFrame: 100 days post DLI
measure: Duration of Complete Response in Months (Maximum 12)
timeFrame: 1 year post DLI
Secondary outcomes:
measure: Acute Graft-versus-host Disease
timeFrame: 100 days post DLI
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Philip L. McCarthy, MD
role: PRINCIPAL_INVESTIGATOR
References: