Adult Acute Megakaryoblastic Leukemia (M7)NCT02105116
AML Therapy With Irradiated Allogeneic Cells
A study testing fludarabine phosphate, cytarabine and donor lymphocytes in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial summary
This pilot clinical trial studies if cells donated by a close genetic relative can help maintain acute myeloid leukemia (AML) complete remission (CR). Eligible patients will receive a standard induction chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
- What is being tested?
- fludarabine phosphate, cytarabine and donor lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to 16 Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven non-M3 AML:
- Refractory/relapsed AML OR
- Initial diagnosis of AML in patient >= 60 years old
- Total bilirubin =< 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
- Cardiac left ventricular ejection fraction (LVEF) >= 35%
Show all 30Show fewer
- Serum creatinine =< 1.5 mg/dl
- Any organ dysfunction thought to be secondary to disease will be considered separately and the patient will be included at the investigators discretion
- Patients must give informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 3
- Must have a potential haploidentical donor (parent, sibling, child)
- A patient is eligible for second enrollment (allo-cellular therapy) if all of the following inclusion criteria are met:
- Patient must have documented CR or CRp after 1 or 2 cycles of fludarabine + cytarabine
- Patient must not be a candidate for an allo-hematopoietic stem cell transplant (HSCT)
- Patient must have a partially (>= 3/6 class I antigen) human leukocyte antigen (HLA)-matched (by serology or low resolution deoxyribonucleic acid [DNA] testing) relative able to serve as a donor
- Patients must not have active uncontrolled infections, other medical or psychological/social conditions that might increase the likelihood of patient adverse effects or poor outcomes
- Total bilirubin < 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)
- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional ULN
- Serum creatinine < 2.0 mg/dl
- ECOG performance status =< 2
- DONOR: donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched
- DONOR: donor must meet all New Brunswick Affiliated Hospitals (NBAH) requirements for hematopoietic stem cell donation, including:
- DONOR: age >= 18 years old
- DONOR: white blood cells (WBC) 4.0-10.0 x 10^3/mm^3
- DONOR: platelet count 150,000 to 440,000/mm^3
- DONOR: hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
- DONOR: not pregnant or lactating
- DONOR: not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by NBAH Blood Center
- DONOR: no uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes
- DONOR: meet other blood bank criteria for blood product donation (as determined by NBAH Blood Center screening history and laboratory studies)
Who cannot join
- History of current or prior medical problems that the investigator feels will prevent administration of therapy or assessment of response due to excess toxicity
- Patients with known active central nervous system (CNS) leukemia will be excluded from this clinical study
- Known HIV-positive patients are excluded from the study
- Patients may not be pregnant or breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
This pilot clinical trial studies if cells donated by a close genetic relative can help maintain acute myeloid leukemia (AML) complete remission (CR). Eligible patients will receive a standard induction chemotherapy. If a complete remission results they will receive irradiated allogeneic cells from a HLA haploidentical relative. Only patients who obtain a CR after the standard induction chemotherapy are eligible for the experimental therapy (irradiated haploidentical cells).
Read the detailed description
PRIMARY OBJECTIVES:
- Toxicity of haploidentical allogeneic cellular therapy in patients in complete remission (CR) (or CR with incomplete platelet recovery [CRp]) after induction chemotherapy with fludarabine (fludarabine phosphate)-cytarabine.
II. Efficacy of haploidentical allogeneic cellular therapy in patients in CR (or CRp) after induction chemotherapy with fludarabine-cytarabine (remission rates at 6, 12, 18, 24 months).
SECONDARY OBJECTIVES:
- Immunologic parameters before and after haploidentical therapy: host anti-leukemia T cells; host regulatory T cells.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 1 hour once daily (QD) for 5 days and cytarabine IV over 4 hours for 5 days. Treatment may continue for 1 or 2 courses at the discretion of the treating physician.
ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated donor lymphocyte infusion (DLI) of 3 x 10^8 cluster of differentiation (CD)3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 2 years.
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Being tested
- fludarabine phosphate, cytarabine, donor lymphocytes, laboratory biomarker analysis, G-CSF
- Medical subject headings
- Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV
donor lymphocytesBiological
Undergo infusion of donor lymphocytes
laboratory biomarker analysisOther
Correlative studies
G-CSFDrug
Also called Filgrastim, Neupogen®
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Standard chemotherapy followed by allogenic therapy | Experimental | INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: fludarabine phosphate; Drug: cytarabine; Biological: donor lymphocytes; Other: laboratory biomarker analysis; Drug: G-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Related to Experimental Therapy
Patients will be observed for incidence of adverse events related to experimental therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study because of failure to reach complete remission. None of the enrolled patients received experimental therapy (allogeneic donor lymphocyte therapy). The one death occurred while receiving standard therapy prior to eligibility for experimental allogeneic therapy. The remained of patients were ineligible for experimental therapy because they did not obtain a complete remission after standard induction chemotherapy.
Measured: Up to 2 years
Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
Patients' response rate will be determined by allogeneic cell therapy-related mortality. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
Measured: Up to 2 years
Response Rate, Determined by Duration of Complete Remission
Patients will be scored as being in continuous remission at 2 years or having relapsed sooner. Of the 6 patients enrolled, all were ineligible to enter the treatment phase of the study for failure to reach complete remission for allogenic treatment.
Measured: Up to 2 years
Secondary outcomes (1)
Progression Free Survival Probability for CR
Calculated using Kaplan-Meier estimation method. Corresponding 95% confidence interval will be provided. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
Measured: At 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study startFeb 2014
- Primary completion16 Dec 2015
- Study completion16 Dec 2015
Why it stopped: No patients were eligible to receive the experimental component of the protocol therapy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Responsible party
- Principal investigator, Roger Strair, MD, PhD, Rutgers Cancer Institute of New Jersey
- Investigators
- Roger Strair, MD, PhD, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02105116
- Sponsor's protocol ID
- Pro2013002693
- Other IDs
- NCI-2013-02408, Pro2013002693, 021208, P30CA072720
- Status last verified
- Aug 2021
- First submitted
- 2 Apr 2014
- Last updated
- 24 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AML Therapy With Irradiated Allogeneic Cells
- ClinicalTrials.gov ID
- NCT02105116
- Acronym / sponsor ID
- Pro2013002693
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No patients were eligible to receive the experimental component of the protocol therapy.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Study start
- Feb 2014
- Primary completion
- 16 Dec 2015 (actual)
- Study completion
- 16 Dec 2015 (actual)
- First posted
- 7 Apr 2014 (estimated)
- Results
- Posted 26 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies if cells donated by a close genetic relative can help maintain acute myeloid leukemia (AML) complete remission (CR). Eligible patients will receive a standard induction chemotherapy. If a complete remission results they will receive irradiated allogeneic cells from a HLA haploidentical relative. Only patients who obtain a CR after the standard induction chemotherapy are eligible for the experimental therapy (irradiated haploidentical cells).
Detailed description
PRIMARY OBJECTIVES:
- Toxicity of haploidentical allogeneic cellular therapy in patients in complete remission (CR) (or CR with incomplete platelet recovery [CRp]) after induction chemotherapy with fludarabine (fludarabine phosphate)-cytarabine.
II. Efficacy of haploidentical allogeneic cellular therapy in patients in CR (or CRp) after induction chemotherapy with fludarabine-cytarabine (remission rates at 6, 12, 18, 24 months).
SECONDARY OBJECTIVES:
- Immunologic parameters before and after haploidentical therapy: host anti-leukemia T cells; host regulatory T cells.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 1 hour once daily (QD) for 5 days and cytarabine IV over 4 hours for 5 days. Treatment may continue for 1 or 2 courses at the discretion of the treating physician.
ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated donor lymphocyte infusion (DLI) of 3 x 10^8 cluster of differentiation (CD)3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard chemotherapy followed by allogenic therapy | Experimental | Drug: fludarabine phosphate, Drug: cytarabine, Biological: donor lymphocytes, Other: laboratory biomarker analysis, Drug: G-CSFINDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Histologically proven non-M3 AML:
- Total bilirubin =< 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
- Cardiac left ventricular ejection fraction (LVEF) >= 35%
- Serum creatinine =< 1.5 mg/dl
Key exclusion criteria (4 listed)
- History of current or prior medical problems that the investigator feels will prevent administration of therapy or assessment of response due to excess toxicity
- Patients with known active central nervous system (CNS) leukemia will be excluded from this clinical study
- Known HIV-positive patients are excluded from the study
- Patients may not be pregnant or breast feeding
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 |
|---|---|---|
| fludarabine phosphateAlso: 2-F-ara-AMP, Beneflur, FludaraGiven IV | Drug | Standard chemotherapy followed by allogenic therapy |
| cytarabineAlso: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-UGiven IV | Drug | Standard chemotherapy followed by allogenic therapy |
| donor lymphocytesUndergo infusion of donor lymphocytes | Biological | Standard chemotherapy followed by allogenic therapy |
| laboratory biomarker analysisCorrelative studies | Other | Standard chemotherapy followed by allogenic therapy |
| G-CSFAlso: Filgrastim, Neupogen®Given IV | Drug | Standard chemotherapy followed by allogenic therapy |
Primary outcome
Adverse Events Related to Experimental Therapy
Time frame: Up to 2 years
Patients will be observed for incidence of adverse events related to experimental therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study because of failure to reach complete remission. None of the enrolled patients received experimental therapy (allogeneic donor lymphocyte therapy). The one death occurred while receiving standard therapy prior to eligibility for experimental allogeneic therapy. The remained of patients were ineligible for experimental therapy because they did not obtain a complete remission after standard induction chemotherapy.
Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
Time frame: Up to 2 years
Patients' response rate will be determined by allogeneic cell therapy-related mortality. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
Response Rate, Determined by Duration of Complete Remission
Time frame: Up to 2 years
Patients will be scored as being in continuous remission at 2 years or having relapsed sooner. Of the 6 patients enrolled, all were ineligible to enter the treatment phase of the study for failure to reach complete remission for allogenic treatment.
1 secondary outcome
Progression Free Survival Probability for CR
Time frame: At 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 study testing fludarabine phosphate, cytarabine and donor lymphocytes in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Rutgers, The State University 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?
The sponsor lists 30 inclusion and 4 exclusion criteria. 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 24 Aug 2021. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Adverse Events Related to Experimental Therapy (time frame: Up to 2 years). The study lists 3 primary outcomes in all. 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 24 Aug 2021.