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.
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
- Conditions the study is for
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- 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
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 group | Role | What they receive |
|---|---|---|
| Irradiated allogeneic lymphocytes after Total Body Irradiation | Experimental | Not 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.
Toxicity
Measured: 3 years
Secondary outcomes (3)
Immunologic parameters before and after haploidentical therapy
Measured: 3 years
Anti-tumor activity and/or duration of remission in those patients who enter the study in second complete remission or greater
Measured: 3 years
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.
- First posted16 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionNov 2011
- Study completionNov 2011
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- University of Medicine and Dentistry of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Roger Strair, MD, PhD, Principal investigator, Rutgers Cancer Institute of New Jersey
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
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation
- ClinicalTrials.gov ID
- NCT00996359
- Acronym / sponsor ID
- 020901
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Medicine and Dentistry of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 16 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irradiated allogeneic lymphocytes after Total Body Irradiation | Experimental | Biological: Irradiated haploidentical allogeneic lymphocytes, Radiation: total-body irradiation |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irradiated haploidentical allogeneic lymphocytesPartially HLA-matched irradiated donor lymphocytes will be infused after total body irradiation. | Biological | Irradiated allogeneic lymphocytes after Total Body Irradiation |
| total-body irradiation100 cGy TBI | Radiation | Irradiated allogeneic lymphocytes after Total Body Irradiation |
Primary outcome
Toxicity
Time frame: 3 years
3 secondary outcomes
Immunologic parameters before and after haploidentical therapy
Time frame: 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
Treatment-related mortality
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger Strair, MD, PhD principal investigator
Rutgers Cancer Institute of New Jersey
1 site in 1 country: see every site and its status.
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.