Know Cancer

or
forgot password

Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation


N/A
13 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Thank you

Trial Information

Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation


OBJECTIVES:

Primary

- To evaluate the toxicity of irradiated haploidentical allogeneic cellular therapy after
low-dose total-body irradiation and no pharmacologic graft-vs-host disease prophylaxis
in patients with relapsed or refractory hematologic malignancies or patients with acute
myeloid leukemia (AML) or acute lymphoblastic leukemia in second or greater complete
remission (CR2).

Secondary

- To evaluate immunologic parameters before and after haploidentical therapy.

- To demonstrate host anti-leukemia T-cells in a subset of patients with AML who are
HLA-A2-positive.

- To observe any evidence of antitumor activity within the confines of this pilot study
and/or assess the duration of remission in those patients who enter the study in CR2.

OUTLINE: Patients undergo low-dose total-body irradiation and infusion of irradiated donor
cells on day 0. Patients also receive filgrastim subcutaneously (SC) daily or pegfilgrastim
SC every 14 days starting on day 1.

Patients in complete remission (CR) or with persistent disease undergo irradiated donor
lymphocyte infusion (DLI) at 8 weeks. Repeat irradiated DLI is administered if patients
remain in CR or achieve stable or responding disease after the second infusion (if confirmed
by histologic assessment) or third infusion (if confirmed by radiographic assessment). DLI
repeats every 8 weeks pending disease and clinical status up to a total of 6 infusions over
a 12-month period.

Blood samples are collected at baseline, upon recovery of counts, and then monthly
thereafter for immunologic studies.

After completion of study treatment, patients are followed up periodically.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity

Outcome Time Frame:

3 years

Safety Issue:

Yes

Principal Investigator

Roger Strair, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey

Authority:

United States: Food and Drug Administration

Study ID:

020901

NCT ID:

NCT00996359

Start Date:

October 2009

Completion Date:

November 2011

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • 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
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903