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

September 13, 2013 updated by: University of Medicine and Dentistry of New Jersey

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Irradiated allogeneic lymphocytes 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Toxicity
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Immunologic parameters before and after haploidentical therapy
Time Frame: 3 years
3 years
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
3 years
Treatment-related mortality
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Medicine and Dentistry of New Jersey

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

October 15, 2009

First Submitted That Met QC Criteria

October 15, 2009

First Posted (Estimate)

October 16, 2009

Study Record Updates

Last Update Posted (Estimate)

September 17, 2013

Last Update Submitted That Met QC Criteria

September 13, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020901 (Bridgeport Hospital)
  • P30CA072720 (U.S. NIH Grant/Contract)
  • CDR0000656757 (Other Identifier: NIH)
  • IRB# 0220090213

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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