Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

This pilot clinical trial studies the side effects of irradiated donor cells following stem cell transplant in controlling cancer in patients with hematologic malignancies. Transfusion of irradiated donor cells (immune cells) from relatives may cause the patient's cancer to decrease in size and may help control cancer in patients receiving a stem cell transplant.

PRIMARY OBJECTIVES:

I. To determine the toxicity associated with the administration of irradiated haploidentical cells (IHC) to patients with high-risk hematologic malignancies.

SECONDARY OBJECTIVES:

I. To determine if there is evidence of disease response associated with IHC.

TERTIARY OBJECTIVES:

I. To determine if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Within 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous hematopoietic stem cell transplantation (HSCT), patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

COHORT II: Patients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

After completion of study treatment, patients will be followed up within 8 weeks.

Eligibility Criteria:
Inclusion Criteria:

* Patient with disease (stage) eligible per cohort
* COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue and ?high-risk? disease as defined below:

  * Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified World Health Organization \[WHO\] subtypes) not in computed tomography (CT)-positron emission tomography (PET) complete remission at time of high dose therapy
  * Diffuse large cell lymphoma with ?double hit? or ?double expressor? features
  * Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO specified subtypes) refractory to standard induction therapy OR relapsing within 1 year of treatment OR in greater that second complete remission (CR)
  * Mantle cell lymphoma not in CR1
  * Multiple myeloma with ONE (or more) of the following high risk features:

    * Less than very good partial remission at time of high dose therapy
    * High Revised-International Staging System (R-ISS) (stage III ? 2 microglobulin \>= 5.5 plus lactate dehydrogenase \[LDH\] \> upper limit of normal \[ULN\] and/or del17p, t(4;14), t(14;16)) at time of diagnosis
    * Cytogenetics or fluorescent in situ hybridization (FISH) del17p
* COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:

  * Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network \[ELN\]) at presentation

    * Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics)
  * AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction \[PCR\] for NPM1, core-binding factor \[CBF\], mixed lineage leukemia \[MLL\]) or flow cytometry
  * AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi)
  * Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation
  * Treatment-related MDS or AML
  * Acute lymphoblastic leukemia (ALL) not in CR1
  * ALL with MRD
  * Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant
  * Multiple myeloma
  * Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant
  * Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse \> 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
* Availability of a genetic child, genetic parent or sibling as a potential HLA haploidentical donor
* Meets standard eligibility requirements for high dose chemotherapy with autologous stem cell rescue (COHORT 1) or allogeneic hematopoietic stem cell transplant (COHORT 2) and has signed consent for those procedures
* DONOR: Donor must be related to patient and be partially (\>= 3/6 antigen) HLA-matched
* DONOR: Donor must meet all Robert Wood Johnson (RWJ) Blood Services requirements for hematopoietic stem cell donation including:

  * Age \>= 18 years old;
  * Normal hemogram (white blood cells \[WBC\] 4.0-10.0 x 10\^3/mm\^3; platelet count 150,000 to 440,000/mm\^3 ; hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
  * Not pregnant or lactating;
  * Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-cell lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by RWJ Blood Services;
  * No uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes;
  * Meet other blood bank criteria for blood product donation (as determined by RWJ Blood Center screening history and laboratory studies)

Exclusion Criteria:

* Non-English speaking person
* Patients undergoing haploidentical allogeneic hematopoietic stem cell transplants are not eligible; patients undergoing \< 10/10 HLA allele matched allogeneic transplant are not eligible
* Pregnant women
* DONOR: Non-English speaking person
* DONOR: Pregnant women