Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04539236|
Recruitment Status : Recruiting
First Posted : September 4, 2020
Last Update Posted : September 30, 2022
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Drug: Lenalidomide Drug: Luspatercept||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Phase Ib/II Study That Combines Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients|
|Actual Study Start Date :||November 9, 2021|
|Estimated Primary Completion Date :||August 1, 2029|
|Estimated Study Completion Date :||August 1, 2029|
Experimental: Luspatercept + Lenalidomide Group
Phase 1B: Luspatercept will be administered at starting dose 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered in a dose escalation design between 3 cohorts to determine MTD (2.5 mg, 5 mg and 10 mg daily dose on a 21-day cycle). MTD will be defined as the dose level with 0 or 1 DLT out of 6 participants. MTD will be declared as the RP2D for the Phase II portion of the study.
Phase II: Luspatercept will be administered at 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered with the RP2D daily for 21 days on a 21 day cycle.
Treatment with combination of Lenalidomide and Luspatercept will continue as long as a participant is deriving clinical benefit, in the opinion of the treating physician, for up to 5 years or until disease progression or treatment intolerance.
Administered daily by mouth on a 21 day cycle. Doses will be administered at 2.5 mg, 5 mg and 10 mg.
Other Name: Revlimid
Administered subcutaneously in the upper arm, thigh and/or abdomen on Day 1 of a 21 day cycle. Starting dose will be at 1.0 mg/kg and can be titrated, dependent on participant response, to doses of 1.33 mg/kg, and 1.75 mg/kg.
- MTD/RP2D of Luspatercept combined with Lenalidomide [ Time Frame: Up to 15 weeks ]Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Luspatercept combined with Lenalidomide (reported in mg/kg) from Phase Ib portion of study
- DLT Rate for Phase Ib [ Time Frame: Up to 15 weeks ]DLT rate is defined as the percentage of participants with Dose Limiting Toxicities (DLT) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs are non-hematologic events grade 3 or higher that are at least possibly related to the investigational product and do not resolve to grade 1 or lower within 21 days.
- Percentage of participants with RBC-TI response [ Time Frame: Up to 5 years ]Red Blood Cell Transfusion Independence (RBC-TI) response is defined as participants who are RBC transfusion free over any consecutive 56-day period
- Toxicity Rate for Phase II [ Time Frame: Up to 5 years ]Toxicity rate is defined as the percentage of participants with treatment emergent adverse events (TE-AEs) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
- Percentage of participants with relevant reduction in RBC transfusion requirement [ Time Frame: Up to 5 years ]Participants with relevant reduction in RBC transfusion requirement will be defined as those participants whose total number of RBC units transfused has decreased by at least 4 units compared to the number transfused during the 8 weeks before study participation
- Percentage of participants with Erythroid Response [ Time Frame: Up to 5 years ]Hematologic Improvement Erythroid Response (HI-E) will bdefined as at least a 1.5 g/dl increase in serum hemoglobin from baseline
- Duration of RBC-TI [ Time Frame: Up to 5 years ]The length of time where participants are RBC transfusion free will be reported
- Percentage of participants with Platelet Response [ Time Frame: Up to 5 years ]
Hematologic improvement Platelet response (HI-P) will be defined as:
For participants with a serum baseline platelet count of > 20,000/mm3 at baseline: An absolute increase of ≥ 30,000/mm3 from baseline
For participants with a serum platelet count ≤ 20,000/mm3 at baseline: An increase of at least 100% from baseline counts to a platelet count > 20,000/mm3.
- Percentage of participants with Neutrophil Response [ Time Frame: Up to 5 years ]Hematologic improvement of Neutrophil Response (HI-N) will be defined as a serum absolute neutrophil count (ANC) increase from baseline of at least 100%, and an absolute increase of > 500/mm3 from baseline.
- Percentage of participants experiencing a progression to higher-risk MDS or AML [ Time Frame: Up to 5 years ]Percentage of participants experiencing a progression to higher-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)
- Overall Survival (OS) [ Time Frame: Up to 5 years ]OS is calculated for all participants from the date of initial registration to date of death due to any cause. The follow-up for participants last known to be alive is censored at the date of last contact.
- Percentage of participants with RBC-TI lasting 16 weeks [ Time Frame: Up to 5 years ]Percentage of participants with RBC-TI lasting 16 weeks (112 days) will be assessed per the Blood 2019 position paper on defining response in lower-risk MDS
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04539236
|Contact: Mikkael Sekeres, MDemail@example.com|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Mikkael Sekeres, MD 305-243-9974 firstname.lastname@example.org|
|Principal Investigator: Mikkael Sekeres, MD|
|Moffitt Cancer Center||Not yet recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Rami Komrokji, MD 813-745-4291 email@example.com|
|Principal Investigator: Rami Komrokji, MD|
|United States, Maryland|
|Johns Hopkins University||Not yet recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Amy DeZern, MD 410-502-7208 firstname.lastname@example.org|
|Principal Investigator: Amy DeZern, MD|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Not yet recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Rich Stone, MD 617-632-2214 email@example.com|
|Principal Investigator: Rich Stone, MD|
|United States, New York|
|Cornell University||Not yet recruiting|
|New York, New York, United States, 10021|
|Contact: Gail Roboz, MD 646-962-2700 firstname.lastname@example.org|
|Principal Investigator: Gail Roboz, MD|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|Contact: Hetty Carraway, MD 216-218-6828 email@example.com|
|Principal Investigator: Hetty Carraway, MD|
|Principal Investigator:||Mikkael Sekeres, MD||University of Miami|