Donor Stem Cell Transplant After Total-Body Irradiation in Treating Patients With Relapsed or Refractory Hematologic Cancer or Acute Myeloid Leukemia or Acute Lymphocytic Leukemia in Complete Remission
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Purpose
RATIONALE: Giving low-dose total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant after total-body irradiation and to see how well it works in treating patients with relapsed or refractory hematologic cancer or acute myeloid leukemia or acute lymphocytic leukemia in complete remission.
| Condition | Intervention |
|---|---|
|
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes |
Biological: Irradiated haploidentical allogeneic lymphocytes Radiation: total-body irradiation |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation |
- Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Treatment-related mortality [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Immunologic parameters before and after haploidentical therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Anti-tumor activity and/or duration of remission in those patients who enter the study in second complete remission or greater [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Enrollment: | 4 |
| Study Start Date: | October 2009 |
| Study Completion Date: | November 2011 |
| Primary Completion Date: | November 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Allogeneic Cellular Therapy after Total Body Irradiation |
Biological: Irradiated haploidentical allogeneic lymphocytes
Partially HLA-matched irradiated donor lymphocytes will be infused after total body irradiation.
Radiation: total-body irradiation
100 cGy TBI
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 13 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New Jersey | |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | |
| New Brunswick, New Jersey, United States, 08903 | |
| Principal Investigator: | Roger Strair, MD, PhD | Cancer Institute of New Jersey |
More Information
Additional Information:
No publications provided
| Responsible Party: | University of Medicine and Dentistry New Jersey |
| ClinicalTrials.gov Identifier: | NCT00996359 History of Changes |
| Other Study ID Numbers: | 020901, P30CA072720, CDR0000656757, IRB# 0220090213 |
| Study First Received: | October 15, 2009 |
| Last Updated: | June 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Medicine and Dentistry New Jersey:
|
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 |
Additional relevant MeSH terms:
|
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 Neoplasms by Histologic Type |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Bone Marrow Diseases Precancerous Conditions Lymphoma, Non-Hodgkin |
ClinicalTrials.gov processed this record on May 19, 2013