Acute Myeloid Leukemia (AML)Phase 1NCT02255162
Lenalidomide in Combination With Microtransplantation as Post-remission Therapy in AML
A Phase 1 study testing Lenalidomide, HLA-mismatched stem-cell Microtransplantation and Cytarabine in people with Acute Myeloid Leukemia (AML) and Acute Myelocytic Leukemia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study is evaluating the safety and tolerability of the drug lenalidomide in combination with and following mismatched related donor microtransplantation in high risk AML patients in first remission. This study also aims to define the maximum tolerated dose (MTD) of lenalidomide given in this setting. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia
- What is being tested?
- Lenalidomide, HLA-mismatched stem-cell Microtransplantation and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Dec 2016
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Recipient Inclusion Criteria
- Adults, aged 18 through 75 years of age, with pathologically confirmed acute myelogenous leukemia, in pathologically confirmed complete remission following anti-leukemic therapy.
- AST, ALT and Alkaline Phosphatase <5x Upper Limit normal (ULN), direct bilirubin < 2.0 mg/dl.
- Adequate renal function as defined by: calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault Formula) or serum Cr less than institution ULN (the elderly will often have < 60 GFR)
- ECOG performance status 0-2.
- Have a diagnosis of high-risk AML as established by a poor-risk karyotype, adverse risk by ELN criteria, a therapy-related AML, age ≥ 60 or with antecedent hematologic disorder
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- LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram
- Patients, or appropriate designee, must be able to provide informed consent.
- Must not have received systemic anti-neoplastic therapy, including radiotherapy within 14 days of study treatment.
- Female patients of childbearing age must have negative pregnancy test.
- Male subject agrees to use an acceptable method for contraception during the entire study treatment period and through 6 months after the last dose of lenalidomide.
- All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. If needed, patients should be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation.
- Donor Inclusion Criteria
- Haploidentical 1st-degree relative as defined by 3/6 or 4/6 HLA-matched at HLA -A, -B, or -DRB1 who is 18-70 years of age
- ECOG performance status 0 or 1
- Excellent health per conventional pre-donor history (medical and psychosocial evaluation)
- No positive testing for viral infection (HbsAg, HIV, HCV)
- Donor ability to understand and provide informed consent
- Meets standard institutional criteria for GCSF mobilized PBSC donation
Who cannot join
- Recipient Exclusion Criteria
- Diagnosis of acute promyelocytic leukemia
- Active refractory or relapsed acute leukemia
- Prior use of fludarabine, as this agent has been associated with higher subsequent rates of graft versus host disease
- Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
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- HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drug. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- A diagnosis of active hepatitis B or C as defined by detectable viral load assays in the blood
- Known hypersensitivity to thalidomide or lenalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking lenalidomide.
- Significant cardiac disease as determined by the investigator including:
- Known or suspected cardiac amyloidosis
- Congestive heart failure of Class III or IV of the NYHA classification
- Uncontrolled angina, hypertension or arrhythmia
- Myocardial infarction in past 6 months
- Any uncontrolled or severe cardiovascular disease
- Prior cerebrovascular event with persistent neurologic deficit
- Medical conditions that, in the investigator's opinion, would impose excessive risk to the subject.
- Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy.
- Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.
- Pregnant women are excluded from this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)
This research study is evaluating the safety and tolerability of the drug lenalidomide in combination with and following mismatched related donor microtransplantation in high risk AML patients in first remission. This study also aims to define the maximum tolerated dose (MTD) of lenalidomide given in this setting.
Microtransplantation seeks to give the participant donor cells in hopes that those cells can attack the underlying cancer. However, since the donor cells do not replace all of the host cells, it can hopefully avoid many of the serious risks involved with standard transplant, including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the participant's normal body. Recent studies have suggested that lenalidomide can help aid donor cells to attack cancer when given after a stem cell transplant. This trial is trying to see if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part of microtransplantation.
The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been approved for other uses such as in the treatment of other cancers including multiple myeloma and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact antitumor mechanism of action of lenalidomide is unknown.
Read the detailed description
After the screening procedures confirm that the participant is eligible to participate in the research study. The participant will be given a study drug-dosing calendar.
The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses. Participants will receive the following:
- Cytarabine
- Microtransplantation
- Lenalidomide
- Conditions
- Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Granulocytic Leukemia, Acute Non-Lymphocytic Leukemia
- Being tested
- Lenalidomide, HLA-mismatched stem-cell Microtransplantation, Cytarabine
- Keywords
- Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Granulocytic Leukemia, Acute Non-Lymphocytic Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called •Revlimid®
Patients will receive lenalidomide starting on day 6 of each post-remission cycle, following conclusion of cytarabine post-remission therapy on days 1-5. Following count recovery in the third post-remission cycle, patients will then receive lenalidomide daily as a maintenance therapy.
HLA-mismatched stem-cell MicrotransplantationGenetic
Patient will receive HLA-mismatched stem cell microtransplant infusion on day 6 of each post-remission cycle, following conclusion of course of cytarabine in each cycle.
CytarabineDrug
Also called Cytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside
Patients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide | Experimental | Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.
Participants will receive the following:
* Cytarabine-intravenous, fixed dosage, given 5 times during cycle
* HLA-mismatched stem-cell microtransplantation
* Lenalidomide-administered daily per cycle Receives: Drug: Lenalidomide; Genetic: HLA-mismatched stem-cell Microtransplantation; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
Measured: Baseline, 42 Days
Secondary outcomes (5)
Disease Free Survival
Measured: 1 year
Overall Survival
Measured: 1 Year
To assess immunomodulatory effects of this combination through measurement of T cell subsets by flow cytometric techniques and through microchimerism analysis at multiple points on study
Measured: 2 Years
To identify incidence and severity of acute and chronic graft versus host disease (GVHD).
Measured: 2 Years
To detect and categorize, according to severity, the cumulative incidences of toxicities
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2016
- Study completionDec 2016
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 Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Principal investigator, Amir Fathi, Massachusetts General Hospital
- Investigators
- Amir Fathi, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02255162
- Sponsor's protocol ID
- 14-265
- Status last verified
- Aug 2017
- First submitted
- 26 Sep 2014
- Last updated
- 18 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT02255162
- Acronym / sponsor ID
- 14-265
- Conditions
- Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Granulocytic Leukemia, Acute Non-Lymphocytic Leukemia
- Keywords
- Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Granulocytic Leukemia, Acute Non-Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Jan 2015 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 2 Oct 2014 (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.
This research study is evaluating the safety and tolerability of the drug lenalidomide in combination with and following mismatched related donor microtransplantation in high risk AML patients in first remission. This study also aims to define the maximum tolerated dose (MTD) of lenalidomide given in this setting.
Microtransplantation seeks to give the participant donor cells in hopes that those cells can attack the underlying cancer. However, since the donor cells do not replace all of the host cells, it can hopefully avoid many of the serious risks involved with standard transplant, including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the participant's normal body. Recent studies have suggested that lenalidomide can help aid donor cells to attack cancer when given after a stem cell transplant. This trial is trying to see if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part of microtransplantation.
The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been approved for other uses such as in the treatment of other cancers including multiple myeloma and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact antitumor mechanism of action of lenalidomide is unknown.
Detailed description
After the screening procedures confirm that the participant is eligible to participate in the research study. The participant will be given a study drug-dosing calendar.
The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses. Participants will receive the following:
- Cytarabine
- Microtransplantation
- Lenalidomide
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide | Experimental | Drug: Lenalidomide, Genetic: HLA-mismatched stem-cell Microtransplantation, Drug: CytarabineDose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Participants will receive the following: * Cytarabine-intravenous, fixed dosage, given 5 times during cycle * HLA-mismatched stem-cell microtransplantation * Lenalidomide-administered daily per cycle |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Recipient Inclusion Criteria
- Adults, aged 18 through 75 years of age, with pathologically confirmed acute myelogenous leukemia, in pathologically confirmed complete remission following anti-leukemic therapy.
- AST, ALT and Alkaline Phosphatase <5x Upper Limit normal (ULN), direct bilirubin < 2.0 mg/dl.
- Adequate renal function as defined by: calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault Formula) or serum Cr less than institution ULN (the elderly will often have < 60 GFR)
- ECOG performance status 0-2.
Key exclusion criteria (21 listed)
- Recipient Exclusion Criteria
- Diagnosis of acute promyelocytic leukemia
- Active refractory or relapsed acute leukemia
- Prior use of fludarabine, as this agent has been associated with higher subsequent rates of graft versus host disease
- Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
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 |
|---|---|---|
| LenalidomideAlso: •Revlimid®Patients will receive lenalidomide starting on day 6 of each post-remission cycle, following conclusion of cytarabine post-remission therapy on days 1-5. Following count recovery in the third post-remission cycle, patients will then receive lenalidomide daily as a maintenance therapy. | Drug | Lenalidomide |
| HLA-mismatched stem-cell MicrotransplantationPatient will receive HLA-mismatched stem cell microtransplant infusion on day 6 of each post-remission cycle, following conclusion of course of cytarabine in each cycle. | Genetic | Lenalidomide |
| CytarabineAlso: Cytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinosidePatients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle. | Drug | Lenalidomide |
Primary outcome
Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
Time frame: Baseline, 42 Days
5 secondary outcomes
Disease Free Survival
Time frame: 1 year
Overall Survival
Time frame: 1 Year
To assess immunomodulatory effects of this combination through measurement of T cell subsets by flow cytometric techniques and through microchimerism analysis at multiple points on study
Time frame: 2 Years
To identify incidence and severity of acute and chronic graft versus host disease (GVHD).
Time frame: 2 Years
To detect and categorize, according to severity, the cumulative incidences of toxicities
Time frame: 2 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 18 Aug 2017.
- Individual participant dataSharing planned: Undecided
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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.
Amir Fathi, MD principal investigator
Massachusetts General Hospital
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 Lenalidomide, HLA-mismatched stem-cell Microtransplantation and Cytarabine in people with Acute Myeloid Leukemia (AML) and Acute Myelocytic Leukemia, run by Massachusetts General Hospital 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 20 inclusion and 21 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 18 Aug 2017. 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?
Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation (time frame: Baseline, 42 Days). 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 18 Aug 2017; AzTrials last refreshed its copy on 3 Nov 2026.