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LeukemiaPhase 1NCT00996359

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

A Phase 1 study testing Irradiated haploidentical allogeneic lymphocytes and total-body irradiation in people with Leukemia and Lymphoma, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 13 years and older
What is being tested?
Irradiated haploidentical allogeneic lymphocytes and total-body irradiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
Oct 2009to Nov 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

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.

Read the 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.

Being tested
Irradiated haploidentical allogeneic lymphocytes, total-body irradiation
Keywords
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
Medical subject headings
Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Irradiated haploidentical allogeneic lymphocytesBiological

    Partially HLA-matched irradiated donor lymphocytes will be infused after total body irradiation.

  • total-body irradiationRadiation

    100 cGy TBI

Study groups in NCT00996359
Study groupRoleWhat they receive
Irradiated allogeneic lymphocytes after Total Body IrradiationExperimentalNot described
Receives: Biological: Irradiated haploidentical allogeneic lymphocytes; Radiation: total-body irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity

    Measured: 3 years

Secondary outcomes (3)
  1. Immunologic parameters before and after haploidentical therapy

    Measured: 3 years

  2. Anti-tumor activity and/or duration of remission in those patients who enter the study in second complete remission or greater

    Measured: 3 years

  3. Treatment-related mortality

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionNov 2011
  4. Study completionNov 2011

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00996359
Sponsor's protocol ID
020901
Other IDs
P30CA072720, CDR0000656757, IRB# 0220090213
Status last verified
Sep 2013
First submitted
15 Oct 2009
Last updated
17 Sep 2013
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Irradiated haploidentical allogeneic lymphocytes and total-body irradiation in people with Leukemia and Lymphoma, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013.

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