Ibrutinib in Preventing Acute Leukemia in Patients After Reduced-Intensity Conditioning and Stem Cell Transplant
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|ClinicalTrials.gov Identifier: NCT03267186|
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : February 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Biphenotypic Leukemia Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Hematopoietic Cell Transplantation Recipient||Drug: Ibrutinib Other: Laboratory Biomarker Analysis||Phase 2|
I. To reduce the incidence of relapse at 18 months after reduced-intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) in blast crisis from a historical baseline of 45% to 25%, using ibrutinib maintenance therapy.
I. To study the incidence and severity of post-transplant complications in subjects receiving ibrutinib maintenance after allogeneic HCT.
II. To study the incidence of infectious complications in subjects receiving maintenance ibrutinib after allogeneic HCT.
III. To study the impact of ibrutinib maintenance on minimal residual disease after RIC and allogeneic HCT.
IV. To study the impact of maintenance ibrutinib on immune reconstitution and alloreactivity after allogeneic HCT, specifically on Th1/ Th2 polarization, T follicular cell number, T and B cell repertoire, serum immunoglobulin levels, and alloantibody formation.
Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib orally (PO) once daily (QD) for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Ibrutinib Maintenance After Reduced-Intensity Conditioning and Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia|
|Actual Study Start Date :||September 12, 2017|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||March 2020|
Experimental: Prevention (ibrutinib)
Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of relapsed leukemia [ Time Frame: Up to 18 months ]Incidence of relapsed leukemia defined as > 5% leukemic blasts detected in bone marrow or peripheral blood. Participants will also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have < 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.
- Incidence of acute GVHD grades II-IV and III-IV [ Time Frame: At 180 days ]
Incidence of acute GVHD grades II-IV and III-IV will be evaluated according following criteria.
Stage of Acute GvHD was assessed as follows.
- Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea >500 mL/day or upper-gut symptoms with positive histology
- Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea >1000 mL/day.
- Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
- Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: diarrhea > 2500 mL/day or severe abdominal pain with or without ileus
Grade of Acute GvHD was determined as follows.
- Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
- Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
- Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
- Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
- Incidence of chronic GVHD [ Time Frame: At 18 months ]Assessment of chronic GvHD will be performed using the 2015 NIH consensus criteria
- Incidence of detectable minimal residual disease [ Time Frame: At 1 year ]Incidence of detectable minimal residual disease will be assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease will be considered present if > 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.
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): NCT03267186
|Contact: Janet Mcdowellfirstname.lastname@example.org|
|United States, California|
|Stanford University, School of Medicine||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Janet McDowell 650-725-1647 email@example.com|
|Principal Investigator: Andrew Rezvani, MD|
|Principal Investigator:||Andrew Rezvani||Stanford University|