Myeldysplastic Syndrome (MDS)Phase 1NCT01629082
Clofarabine Followed By Lenalidomide for High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia
A Phase 1 study testing Clofarabine and Lenalidomide in people with Myeldysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Several types of blood cancer are associated with poor outcomes including high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML). Many people with MDS, CMML, and AML are not candidates for standard treatments. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myeldysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia, Bone Marrow Diseases
- What is being tested?
- Clofarabine and Lenalidomide
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jun 2012to 27 Jun 2018
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18 years old
- Unequivocal diagnosis of MDS (including chronic myelomonocytic leukemia- CMML) according to WHO criteria with IPSS risk categorization for MDS subjects of intermediate-2 to high confirmed by bone marrow evaluation within 30 days prior to study enrollment
- OR
- Unequivocal diagnosis of AML according to WHO criteria to include secondary and relapsed or refractory disease confirmed by bone marrow evaluation within 30 days prior to study enrollment
- ECOG Performance Status less than or equal to 2
- Must have failed at least one prior therapy before study enrollment
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- Ability to comprehend the investigational nature of the study and provide informed consent
- All study participants must be registered into the mandatory RevAssistRevlimid REMS program, and be willing and able to comply with the requirements of RevAssistRevlimid REMS .
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by RevAssistRevlimid REMS ) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMSTM program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
Who cannot join
- Prior Allogeneic Stem Cell Transplant
- Diagnosis of acute promyelocytic leukemia
- Diagnosis of atypical chronic myeloid leukemia BCR-ABL1 negative, juvenile myelomonocytic leukemia, yelodysplastic/myeloproliferative neoplasm unclassifiable)
- Prior therapy with clofarabine at any dose
- Prior therapy with lenalidomide at doses greater than or equal to 25 milligrams daily
- Clinically significant active infection not responding adequately to therapy
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- HIV Positive
- Uncontrolled concurrent hepatic, renal, cardiac, pulmonary, neurologic, infectious, or metabolic disease of such severity, which in the opinion of the PI, would preclude the subjects s ability to tolerate protocol therapy
- Ejection fraction less than 40% by Echocardiogram or MUGA
- Calculated creatinine clearance less 60 milliliters per minute
- Serum bilirubin greater than 1.5 times upper limit of normal
- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) greater than 3 times upper limit normal
- Decreased oxygen saturation at rest (e.g. pulse oximeter less than 88% or PaO2 less than or equal to 55 millimeters of mercury)
- Patients with any condition that prevents their ability to swallow and retain lenalidomide tablets
- Severe psychiatric illness or complex social situations that would limit the patient s ability to tolerate and/or comply with study requirements
- Current pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clofarabine Followed by Lenalidomide for Treatment of High Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia
Background:
- Several types of blood cancer are associated with poor outcomes including high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML). Many people with MDS, CMML, and AML are not candidates for standard treatments. New types of treatment are needed for these cancers.
- Clofarabine and lenalidomide are anticancer drugs. The first damages cancer cells in the body. The second can alter blood supply to abnormal cells or affect how the immune system attacks these cells. These drugs have been previously tested as treatments for MDS and leukemia. However, they have not been tried as a combination for MDS, CMML, and AML. Researchers want to see if these drugs are safe and effective for these types of cancer.
Read more
Objectives:
- To test the safety and effectiveness of clofarabine and lenalidomide for people with high-risk MDS, CMML, and AML.
Eligibility:
- Individuals at least 18 years of age who have high-risk MDS, CMML, and AML.
- Participants must not be candidates for standard treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and bone marrow samples will be collected.
- Participants will have 5 days of treatment with clofarabine. It will be given through a vein during an inpatient hospital stay. If there are no serious side effects after the infusion, participants will continue treatment as outpatients.
- After 28 days, participants will have a bone marrow biopsy to check their response to treatment.
- After the biopsy, participants will start lenalidomide treatment. Half of the participants will take the drug for 28 days (one treatment cycle). The other half will take it for 56 days (two cycles). More blood tests and biopsies will be used to monitor treatment.
- If there are no serious side effects and the disease does not become worse, participants may keep taking lenalidomide at lower doses for up to 12 more cycles.
Read the detailed description
High risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML) are hetereogeneous myeloid malignancies that are associated with a poor prognosis. Due to advanced age and medical comorbidities, the majority of MDS, CMML, and AML patients are not candidates for potentially curative standard treatments such as allogeneic stem cell transplantation (SCT) or intensive chemotherapy (ICT). New therapeutic approaches that improve response rates, have lesser toxicity, and extend survival are clearly needed for high risk MDS and AML patients.
Clofarabine is a myelosuppressive, second generation purine nucleoside analogue which has shown meaningful efficacy at variable dosing levels for high risk MDS and AML patients with a favorable toxicity profile compared to intensive chemotherapy. Lenalidomide is an oral structural analogue of thalidomide with a complex mechanism of action including immunomodulatory, anti-angiogenic, and direct cytotoxic effects which is a well-established treatment for MDS and has shown agent single efficacy at higher doses for AML. Lenalidomide s therapeutic benefit in AML has been the greatest in patients with low presenting total leukocyte and circulating blast counts. We hypothesize that the initial cytoreductive effects of clofarabine may augment the effectiveness of subsequent lenalidomide therapy and create a favorable immunologic milieu for patients eligible for lenalidomide maintenance therapy. This open-label, single institution phase I trial will evaluate a sequential combination of IV clofarabine with oral lenalidomide for the treatment of high risk MDS, CMML, and AML. Subjects will receive a single course of IV clofarabine (5 milligrams per metered square per day times 5) for cytoreduction. This will be followed by oral lenalidomide consolidation with dose escalation from 25 mg daily for 21/28 days for 1 cycle in the first cohort up to 50 mg daily for 28/28 days for 2 cycles in the fourth cohort. In the absence of dose limiting toxicity or disease progression, Subjects will receive lenalidomide maintenance, starting at a dose of 10 mg daily in 28 day cycles, with dose adjustments, for up to 12 cycles.
The overall objective is to determine the safety of sequential therapy with clofarabine and lenalidomide in subjects with high risk MDS, CMML, and AML. The primary study endpoint will be the toxicity profile of this novel treatment combination in each cohort. Secondary endpoints will include characterization of response and duration, overall survival, and the feasibility of maintenance lenalidomide therapy for responding subjects.
- Conditions
- Myeldysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia, Bone Marrow Diseases, Neutropenia, Acute Myeloid Leukemia (AML)
- Being tested
- Clofarabine, Lenalidomide
- Keywords
- Myelodysplastic Syndromes, Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML)
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Bone Marrow Diseases, Neutropenia, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
LenalidomideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the maximum tolerated dose.
Secondary outcomes (3)
Overall Survival
Characterization of response rate and duration
Feasibility of lenalidomide maintenance therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2012 (estimated)
- Study start6 Jun 2012
- Primary completion27 Oct 2015
- Study completion27 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myeldysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Celgene Corporation
- Investigators
- Sawa Ito, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01629082
- Sponsor's protocol ID
- 120146
- Other IDs
- 12-H-0146
- Status last verified
- 27 Jun 2018
- First submitted
- 22 Jun 2012
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Garcia-Manero G, Fenaux P. Hypomethylating agents and other novel strategies in myelodysplastic syndromes. J Clin Oncol. 2011 Feb 10;29(5):516-23. doi: 10.1200/JCO.2010.31.0854. Epub 2011 Jan 10.
PubMed 21220589Aul C, Gattermann N, Schneider W. Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol. 1992 Oct;82(2):358-67. doi: 10.1111/j.1365-2141.1992.tb06430.x.
PubMed 1419819Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1;112(1):45-52. doi: 10.1182/blood-2008-01-134858. Epub 2008 Apr 28.
PubMed 18443215
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clofarabine Followed by Lenalidomide for Treatment of High Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01629082
- Acronym / sponsor ID
- 120146
- Conditions
- Myeldysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia, Bone Marrow Diseases, Neutropenia, Acute Myeloid Leukemia (AML)
- Keywords
- Myelodysplastic Syndromes, Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- Celgene Corporation
- Study start
- 6 Jun 2012
- Primary completion
- 27 Oct 2015 (actual)
- Study completion
- 27 Jun 2018 (actual)
- First posted
- 27 Jun 2012 (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.
Background:
- Several types of blood cancer are associated with poor outcomes including high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML). Many people with MDS, CMML, and AML are not candidates for standard treatments. New types of treatment are needed for these cancers.
- Clofarabine and lenalidomide are anticancer drugs. The first damages cancer cells in the body. The second can alter blood supply to abnormal cells or affect how the immune system attacks these cells. These drugs have been previously tested as treatments for MDS and leukemia. However, they have not been tried as a combination for MDS, CMML, and AML. Researchers want to see if these drugs are safe and effective for these types of cancer.
Objectives:
- To test the safety and effectiveness of clofarabine and lenalidomide for people with high-risk MDS, CMML, and AML.
Eligibility:
- Individuals at least 18 years of age who have high-risk MDS, CMML, and AML.
- Participants must not be candidates for standard treatments.
Design:
- Participants will be screened with a physical exam and medical history. Blood and bone marrow samples will be collected.
- Participants will have 5 days of treatment with clofarabine. It will be given through a vein during an inpatient hospital stay. If there are no serious side effects after the infusion, participants will continue treatment as outpatients.
- After 28 days, participants will have a bone marrow biopsy to check their response to treatment.
- After the biopsy, participants will start lenalidomide treatment. Half of the participants will take the drug for 28 days (one treatment cycle). The other half will take it for 56 days (two cycles). More blood tests and biopsies will be used to monitor treatment.
- If there are no serious side effects and the disease does not become worse, participants may keep taking lenalidomide at lower doses for up to 12 more cycles.
Detailed description
High risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML) are hetereogeneous myeloid malignancies that are associated with a poor prognosis. Due to advanced age and medical comorbidities, the majority of MDS, CMML, and AML patients are not candidates for potentially curative standard treatments such as allogeneic stem cell transplantation (SCT) or intensive chemotherapy (ICT). New therapeutic approaches that improve response rates, have lesser toxicity, and extend survival are clearly needed for high risk MDS and AML patients.
Clofarabine is a myelosuppressive, second generation purine nucleoside analogue which has shown meaningful efficacy at variable dosing levels for high risk MDS and AML patients with a favorable toxicity profile compared to intensive chemotherapy. Lenalidomide is an oral structural analogue of thalidomide with a complex mechanism of action including immunomodulatory, anti-angiogenic, and direct cytotoxic effects which is a well-established treatment for MDS and has shown agent single efficacy at higher doses for AML. Lenalidomide s therapeutic benefit in AML has been the greatest in patients with low presenting total leukocyte and circulating blast counts. We hypothesize that the initial cytoreductive effects of clofarabine may augment the effectiveness of subsequent lenalidomide therapy and create a favorable immunologic milieu for patients eligible for lenalidomide maintenance therapy. This open-label, single institution phase I trial will evaluate a sequential combination of IV clofarabine with oral lenalidomide for the treatment of high risk MDS, CMML, and AML. Subjects will receive a single course of IV clofarabine (5 milligrams per metered square per day times 5) for cytoreduction. This will be followed by oral lenalidomide consolidation with dose escalation from 25 mg daily for 21/28 days for 1 cycle in the first cohort up to 50 mg daily for 28/28 days for 2 cycles in the fourth cohort. In the absence of dose limiting toxicity or disease progression, Subjects will receive lenalidomide maintenance, starting at a dose of 10 mg daily in 28 day cycles, with dose adjustments, for up to 12 cycles.
The overall objective is to determine the safety of sequential therapy with clofarabine and lenalidomide in subjects with high risk MDS, CMML, and AML. The primary study endpoint will be the toxicity profile of this novel treatment combination in each cohort. Secondary endpoints will include characterization of response and duration, overall survival, and the feasibility of maintenance lenalidomide therapy for responding subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age greater than or equal to 18 years old
- Unequivocal diagnosis of MDS (including chronic myelomonocytic leukemia- CMML) according to WHO criteria with IPSS risk categorization for MDS subjects of intermediate-2 to high confirmed by bone marrow evaluation within 30 days prior to study enrollment
- OR
- Unequivocal diagnosis of AML according to WHO criteria to include secondary and relapsed or refractory disease confirmed by bone marrow evaluation within 30 days prior to study enrollment
- ECOG Performance Status less than or equal to 2
Key exclusion criteria (16 listed)
- Prior Allogeneic Stem Cell Transplant
- Diagnosis of acute promyelocytic leukemia
- Diagnosis of atypical chronic myeloid leukemia BCR-ABL1 negative, juvenile myelomonocytic leukemia, yelodysplastic/myeloproliferative neoplasm unclassifiable)
- Prior therapy with clofarabine at any dose
- Prior therapy with lenalidomide at doses greater than or equal to 25 milligrams daily
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 |
|---|---|---|
| Clofarabine | Drug | – |
| Lenalidomide | Drug | – |
Primary outcome
Identification of the maximum tolerated dose.
3 secondary outcomes
Overall Survival
Characterization of response rate and duration
Feasibility of lenalidomide maintenance therapy
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 17 Dec 2019.
- Background: PubMed 21220589Garcia-Manero G, Fenaux P. Hypomethylating agents and other novel strategies in myelodysplastic syndromes. J Clin Oncol. 2011 Feb 10;29(5):516-23. doi: 10.1200/JCO.2010.31.0854. Epub 2011 Jan 10.
- Background: PubMed 1419819Aul C, Gattermann N, Schneider W. Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol. 1992 Oct;82(2):358-67. doi: 10.1111/j.1365-2141.1992.tb06430.x.
- Background: PubMed 18443215Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1;112(1):45-52. doi: 10.1182/blood-2008-01-134858. Epub 2008 Apr 28.
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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.
Sawa Ito, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 Clofarabine and Lenalidomide in people with Myeldysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 9 inclusion and 16 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: finished, as of the sponsor's last update on 17 Dec 2019. 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?
Identification of the maximum tolerated dose.. 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 NCT01629082, which also lists 3 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 17 Dec 2019.