LeukemiaPhase 1NCT00107354
Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant
A Phase 1 study testing aldesleukin, therapeutic allogeneic lymphocytes and therapeutic autologous lymphocytes in people with Leukemia and Myelodysplastic Syndromes, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop cancer cells from growing. PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia, acute lymphoblastic… Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- aldesleukin, therapeutic allogeneic lymphocytes and therapeutic autologous lymphocytes
- Type of treatment
- Surgery or procedure
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Dec 1998to Aug 2009
- 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 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Undergoing allogeneic hematopoietic stem cell transplantation* from a major histocompatability complex (MHC)-identical related donor for 1 of the following:
- Primary refractory acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)
- AML or ALL beyond first remission
- Therapy-related AML at any stage
- Philadelphia chromosome (bcr-abl)-positive p190-positive ALL at any stage
- Acute leukemia at any stage arising from myelodysplastic syndromes or myeloproliferative disorders, including any of the following:
- Chronic myelomonocytic leukemia
- Chronic myelogenous leukemia
- Polycythemia vera
- Essential thrombocytosis
- Agnogenic myeloid metaplasia with myelofibrosis
- Refractory anemia with excess blasts
- Refractory anemia with excess blasts in transformation NOTE: *Patients must be enrolled on study prior to undergoing transplantation
- Relapsed disease post-transplantation, as evidenced by 1 of the following criteria:
- Morphologic relapse, as defined by 1 or more of the following:
- Peripheral blasts in the absence of growth factor therapy
- Bone marrow blasts > 5% of nucleated cells
- Extramedullary chloroma or granulocytic sarcoma
- Flow cytometric relapse, as defined by the appearance of cells with abnormal immunophenotype consistent with leukemia relapse in the peripheral blood or bone marrow (detected before transplantation)
- Cytogenetic relapse, as defined by the appearance in 1 or more metaphases from bone marrow or peripheral blood cells of either a non-constitutional cytogenetic abnormality detected in at least 1 cytogenetic study performed before transplantation OR a new abnormality known to be associated with leukemia
- Molecular relapse, as defined by 1 of the following:
- 1 or more positive polymerase chain reaction (PCR) assays for clonotypic immunoglobulin heavy chain or T-cell receptor gene rearrangement in patients transplanted for B- or T-cell ALL respectively
- 1 or more positive post-transplantation reverse transcription PCR assays for p190 BCR-ABL mRNA fusion transcripts in patients transplanted for Philadelphia chromosome-positive p190-positive ALL
- No grade III or IV acute graft-versus-host disease (GVHD)**
- No extensive chronic GVHD NOTE: At time of post-transplant relapse
PATIENT CHARACTERISTICS:
Age
- 14 and over (patients < 14 years of age may be eligible if they are deemed to be of sufficient height and weight by the pediatric attending physician)
Performance status
- Karnofsky 60-100% (at time of post-transplant relapse)
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Not specified
Renal
- Not specified
Other
- No preexisting major nonhematopoietic organ toxicity ≥ grade 3 (at time of post-transplant relapse)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Concurrent immunosuppressive steroid therapy for GVHD allowed provided both of the following are true:
- Able to taper steroid dose to < 0.5 mg/kg/day
- No increase of > 1 grade in acute GVHD OR progression of chronic GVHD within 14 days after dose change
Radiotherapy
- Not specified
Surgery
- Not specified
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
About this study
Official title: Phase I Study of Adoptive Immunotherapy With CD8 Minor Histocompatibility (H) Antigen-Specific CTL Clones for Patients With Relapsed of AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant
RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop cancer cells from growing.
PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after donor stem cell transplant.
Read the detailed description
OBJECTIVES:
Primary
- Determine the toxic effects of adoptive immunotherapy comprising CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the persistence of adoptively transfused T cells in vivo and assess their migration to the bone marrow in these patients.
- Determine the anti-leukemic activity of this therapy in these patients.
OUTLINE: This is a pilot, open-label, nonrandomized study.
- Leukapheresis: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) before transplantation. Donors undergo leukapheresis to obtain PBMCs to use as feeder cells for generating adoptive immunotherapy. Patient PBMCs are combined with donor PBMCs and expanded in vitro to generate CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes (CTLs) for adoptive immunotherapy.
- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation. Patients with a morphologic or flow cytometric relapse on or after day 100 post-transplantation proceed to cytoreductive chemotherapy. Patients with a molecular or cytogenetic relapse on or after day 100 post-transplantation proceed directly to adoptive immunotherapy. Patients with relapsed disease before day 100 post-transplantation are eligible to receive adoptive immunotherapy at a later date provided the patient continues to relapse and CTLs are available.
- Cytoreductive chemotherapy: The chemotherapy regimen for each patient is determined after consideration of prior chemotherapy, type of leukemia, and other clinical parameters. Two regimens to consider are:
- Mitoxantrone IV and etoposide IV on days -6 to -2
- High-dose cytarabine IV over 2 hours twice daily on days -6, -4, and -2 Patients achieving a complete remission after completion of cytoreductive chemotherapy proceed to adoptive immunotherapy.
- Adoptive immunotherapy: Within 2-3 days after completion of cytoreductive chemotherapy, patients receive CTLs IV over 1-2 hours on days 0, 4, 11, 21, and 28 in the absence of unacceptable toxicity. Patients with evidence of persistent disease on or after day 35 OR relapsed disease after an initial response to CTLs receive a sixth infusion of CTLs followed, no more than 24 hours later, by interleukin-2 subcutaneously once daily for up 14 total doses in the absence of unacceptable toxicity. Patients with subsequent relapsed disease after day 48 may be eligible for retreatment.
After completion of study treatment, patients are followed with bone marrow aspiration every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 25-30 patients (10-15 with acute myeloid leukemia or myelodysplastic syndromes AND 10-15 with acute lymphoblastic leukemia) will be accrued for this study within 3 years.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- aldesleukin, therapeutic allogeneic lymphocytes, therapeutic autologous lymphocytes, cytarabine, etoposide
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, 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), de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, T-cell adult acute lymphoblastic leukemia, T-cell childhood acute lymphoblastic leukemia, B-cell adult acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, childhood myelodysplastic syndromes
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldesleukinBiological
therapeutic allogeneic lymphocytesBiological
therapeutic autologous lymphocytesBiological
cytarabineDrug
etoposideDrug
mitoxantrone hydrochlorideDrug
allogeneic bone marrow transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Secondary outcomes (3)
In vivo persistence of adoptively transferred T cells
Migration of adoptively transferred T cells to the bone marrow
Antileukemic activity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2005 (estimated)
- Study startDec 1998
- Primary completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Investigators
- Edus H. Warren, MD, PhD, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00107354
- Sponsor's protocol ID
- 1334.00
- Other IDs
- CDR0000407784
- Status last verified
- Sep 2010
- First submitted
- 5 Apr 2005
- Last updated
- 20 Sep 2010
- Results posted
- No
Publications
Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood. 2010 May 13;115(19):3869-78. doi: 10.1182/blood-2009-10-248997. Epub 2010 Jan 13.
PubMed 20071660Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Blood. 2008 May 1;111(9):4817-26. doi: 10.1182/blood-2007-06-096313. Epub 2008 Feb 25.
PubMed 18299450
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Adoptive Immunotherapy With CD8 Minor Histocompatibility (H) Antigen-Specific CTL Clones for Patients With Relapsed of AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT00107354
- Acronym / sponsor ID
- 1334.00
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Study start
- Dec 1998
- Primary completion
- Aug 2009 (actual)
- First posted
- 6 Apr 2005 (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: Biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop cancer cells from growing.
PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after donor stem cell transplant.
Detailed description
OBJECTIVES:
Primary
- Determine the toxic effects of adoptive immunotherapy comprising CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the persistence of adoptively transfused T cells in vivo and assess their migration to the bone marrow in these patients.
- Determine the anti-leukemic activity of this therapy in these patients.
OUTLINE: This is a pilot, open-label, nonrandomized study.
- Leukapheresis: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) before transplantation. Donors undergo leukapheresis to obtain PBMCs to use as feeder cells for generating adoptive immunotherapy. Patient PBMCs are combined with donor PBMCs and expanded in vitro to generate CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes (CTLs) for adoptive immunotherapy.
- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation. Patients with a morphologic or flow cytometric relapse on or after day 100 post-transplantation proceed to cytoreductive chemotherapy. Patients with a molecular or cytogenetic relapse on or after day 100 post-transplantation proceed directly to adoptive immunotherapy. Patients with relapsed disease before day 100 post-transplantation are eligible to receive adoptive immunotherapy at a later date provided the patient continues to relapse and CTLs are available.
- Cytoreductive chemotherapy: The chemotherapy regimen for each patient is determined after consideration of prior chemotherapy, type of leukemia, and other clinical parameters. Two regimens to consider are:
- Mitoxantrone IV and etoposide IV on days -6 to -2
- High-dose cytarabine IV over 2 hours twice daily on days -6, -4, and -2 Patients achieving a complete remission after completion of cytoreductive chemotherapy proceed to adoptive immunotherapy.
- Adoptive immunotherapy: Within 2-3 days after completion of cytoreductive chemotherapy, patients receive CTLs IV over 1-2 hours on days 0, 4, 11, 21, and 28 in the absence of unacceptable toxicity. Patients with evidence of persistent disease on or after day 35 OR relapsed disease after an initial response to CTLs receive a sixth infusion of CTLs followed, no more than 24 hours later, by interleukin-2 subcutaneously once daily for up 14 total doses in the absence of unacceptable toxicity. Patients with subsequent relapsed disease after day 48 may be eligible for retreatment.
After completion of study treatment, patients are followed with bone marrow aspiration every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 25-30 patients (10-15 with acute myeloid leukemia or myelodysplastic syndromes AND 10-15 with acute lymphoblastic leukemia) will be accrued for this study within 3 years.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 14 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 |
|---|---|---|
| aldesleukin | Biological | – |
| therapeutic allogeneic lymphocytes | Biological | – |
| therapeutic autologous lymphocytes | Biological | – |
| cytarabine | Drug | – |
| etoposide | Drug | – |
| mitoxantrone hydrochloride | Drug | – |
| allogeneic bone marrow transplantation | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
Primary outcome
Toxicity
3 secondary outcomes
In vivo persistence of adoptively transferred T cells
Migration of adoptively transferred T cells to the bone marrow
Antileukemic activity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2010.
- Derived from this study: PubMed 20071660Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood. 2010 May 13;115(19):3869-78. doi: 10.1182/blood-2009-10-248997. Epub 2010 Jan 13.
- Derived from this study: PubMed 18299450Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Blood. 2008 May 1;111(9):4817-26. doi: 10.1182/blood-2007-06-096313. Epub 2008 Feb 25.
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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.
Edus H. Warren, MD, PhD principal investigator
Fred Hutchinson Cancer Center
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 aldesleukin, therapeutic allogeneic lymphocytes and therapeutic autologous lymphocytes in people with Leukemia and Myelodysplastic Syndromes, run by Fred Hutchinson Cancer Center 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: finished, as of the sponsor's last update on 20 Sep 2010. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00107354, which also lists 2 linked publications.
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 20 Sep 2010.