Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
About this trial
This is an interventional treatment trial for Leukemia focused on measuring 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, adult acute myeloid leukemia in remission, recurrent adult acute lymphoblastic leukemia, adult acute lymphoblastic leukemia in remission, relapsing chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, chronic myelomonocytic leukemia, recurrent adult diffuse large cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, adult nasal type extranodal NK/T-cell lymphoma, peripheral T-cell lymphoma, hepatosplenic T-cell lymphoma, anaplastic large cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, childhood diffuse large cell lymphoma, recurrent childhood large cell lymphoma, Burkitt lymphoma, childhood immunoblastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood anaplastic large cell lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, recurrent childhood small noncleaved cell lymphoma, childhood nasal type extranodal NK/T-cell lymphoma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Patients over 18 years old must meet the following criteria:
- Histologically confirmed hematologic malignancy and not a candidate for a standard allogeneic transplantation
High-risk disease, including:
- Refractory/relapsed acute myeloid leukemia (AML) or AML in second or greater completion remission (CR2)
- Relapsed or refractory acute lymphoblastic leukemia (ALL) or ALL in CR2
- Tyrosine kinase inhibitor-resistant chronic myelogenous leukemia in chronic, accelerated, or blast crisis
- Fludarabine-resistant chronic lymphocytic leukemia
- High-risk myelodysplastic syndrome (MDS) (i.e., MDS with a score ≥ 1.5 by the International Scoring System)
- Chronic myelomonocytic leukemia
- Relapsed diffuse large cell non-Hodgkin lymphoma (NHL) with measurable disease after (or not eligible for) high-dose chemotherapy/autologous hematopoietic stem cell (HSC) rescue or allogeneic hematopoietic stem cell transplantation (HSCT)
- Relapsed follicular NHL, mantle cell lymphoma, or low-grade histology NHL with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Relapsed or refractory high-grade/aggressive NHL (Burkitt lymphoma, lymphoblastic lymphoma, T-cell lymphoma, NK-like lymphoma) with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Hodgkin lymphoma with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Relapsed or refractory multiple myeloma after (or not eligible for) high-dose chemotherapy/autologous HSC rescue and following salvage therapy with thalidomide, lenalidomide, bortezomib or other FDA-approved multiple myeloma salvage therapies
Patients 13-17 years old must meet the following criteria:
- Histologically confirmed hematologic malignancy and not a candidate for a standard allogeneic transplantation
High-risk disease, including:
- Refractory/relapsed AML or AML in CR2
- Relapsed or refractory ALL or ALL in CR2
- Relapsed diffuse large cell NHL with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Relapsed follicular NHL, mantle cell lymphoma (or low-grade histology NHL) with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Relapsed or refractory high-grade/aggressive NHL (Burkitt lymphoma, lymphoblastic lymphoma, T-cell lymphoma, NK-like lymphoma) with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Hodgkin lymphoma with measurable disease after (or not eligible for) high-dose chemotherapy/autologous HSC rescue or allogeneic HSCT
- Eligible for haploidentical irradiated cellular therapy
- No known active brain metastases or malignant meningitis
- Available partially (≥ 3/6 class I antigen) HLA-matched (by serology) related donor NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2
Karnofsky PS 60-100% (for patients > 16 years) or Lansky PS 60-100% (for patients ≤ 16 years)
- Patients who are unable to walk because of paralysis but who are up in a wheelchair will be considered ambulatory for the purpose of assessing PS
Patients ≥ 18 years:
- Total bilirubin < 1.5 times upper limit of normal (ULN) (unless attributable to Gilbert disease)
- DLCO/alveolar volume > 50%
- Serum creatinine < 2.0 mg/dL
Patients 13-17 years:
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- 13 to < 16 years: 1.5 mg/dL (male) or 1.4 mg/dL (female)
- ≥ 16 years: 1.7 mg/dL (male) or 1.4 mg/dL (female)
- AST/ALT ≤ 2.5 times ULN for age
- Total bilirubin < 2.0 mg/dL (unless attributable to Gilbert syndrome)
- Shortening fraction ≥ 27% by ECHO or ejection fraction ≥ 50% by radionuclide angiogram
FEV_1, forced vital capacity, and DLCO corrected for hemoglobin ≥ 60% by pulmonary function tests (PFTs)
Children unable to cooperate for PFTs must meet the following criteria:
- No evidence of dyspnea at rest
- No exercise intolerance
- No requirement for supplemental oxygen therapy
- Any other organ dysfunction thought to be secondary to disease will be considered separately and the patient will be eligible at the physician's discretion
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception before, during, and for 24 weeks after study treatment
- No known HIV positivity
- No history of current or prior medical problems that, in the investigator's opinion, would prevent administration of study treatment or assessment of response due to excess toxicity
- No active uncontrolled infections or other medical, psychological, or social conditions that might increase the likelihood of patient adverse effects or poor outcomes
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No corticosteroids within 2 weeks before receiving irradiated donor lymphocyte infusion
- No medications that might increase the likelihood of patient adverse effects or poor outcomes
Sites / Locations
- Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
Arms of the Study
Arm 1
Experimental
Irradiated allogeneic lymphocytes after Total Body Irradiation