Selected ongoing clinical trials for CLL with MRD-guided primary endpoints
| Clinicaltrials.gov ID . | Study title . | Primary outcomes . |
|---|---|---|
| NCT05478512 | Front-line VenObi Combination Followed by Ven or VenZan Combination in Patients With Residual Disease: a MRD Tailored Treatment for Young Patients With High-risk CLL (VIS) | • U-MRD at month 9 • U-MRD at month 21 |
| NCT04941716 | Acalabrutinib in Combination With Venetoclax for the Treatment of Refractory or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma | • Rate of U-MRD |
| NCT04501939 | Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax | • Percentage of subjects with U-MRD after 6 months of cirmtuzumab and venetoclax treatment |
| NCT04754035 | Clinical Study With Ibrutinib and Venetoclax for Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (IMPROVE) | • U-MRD rate evaluated by multi-color flow cytometry analysis (limit of detection 10−4) within the treatment period |
| NCT05677919 | Pirtobrutinib and Venetoclax Combined With Minimal Residual Disease Detection for Previously Untreated Chronic Lymphocytic Leukemia, MIRACLE Study | • Success of U-MRD (< 1/104) will be measured by ClonoSEQ in both PB and BM; the proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients; exact binomial 95% confidence intervals for the true rate of U-MRD by ClonoSEQ in both PB and BM after cycle 15 will be calculated |
| NCT05650723 | Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab | • Percentage of total patients that have achieved U-MRD at cycle 16, as assessed via PB and BM aspirate • Percentage of eligible patients that have achieved U-MRD at cycle 23, as assessed via PB and BM aspirate |
| NCT05317936 | Pirtobrutinib (LOXO-305) Consolidation for MRD Eradication in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) Treated With Venetoclax | • Rate of U-MRD in the PB |
| NCT05168930 | Zanubrutinib and Venetoclax in CLL (ZANU-VEN) | • Rate of U-MRD |
| NCT03580928 | Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL (AVO) | • Rate of BM U-MRD complete response |
| NCT04908228 | Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL (FIGHT) | • BM U-MRD (<10−4) at 30 days follow-up |
| NCT02158091 | A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL | • Number of patients who had a U-MRD complete response (CR) 2 months after chemotherapy • Number of patients who experienced a dose limiting toxicity during phase 1 |
| NCT03708003 | Ibrutinib lead-in Followed by Venetoclax Plus Ibrutinib in Patients With RR CLL | • U-MRD CR/CRi at end of cycle 30 |
| NCT04285567 | A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation (CRISTALLO) | • Minimal residual disease (MRD response rate using NGS in the first 140 participants recruited |
| NCT05336812 | Acalabrutinib in Combination With Venetoclax or Obinutuzumab for the Treatment of Treatment-naive Chronic Lymphocytic Leukemia | • Rate of BM U-MRD, defined as tumor cell in 10,000 cells using standard flow-based assay, achieved after completion of therapy |
| NCT04169737 | Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma | • Disease assessment of BM U-MRD (<10−4, MRD4) (TN cohort) • Disease assessment of BM undetectable-MRD4 (RR cohort) |
| NCT04010968 | Evaluation of Risk-Adapted and MRD-Driven Strategy for Untreated Fit Patients With Intermediate Risk Chronic Lymphocytic Leukemia (ERADIC) | • Minimal residual disease (MRD) in BM <0.01% at month 27 |
| NCT05791409 | Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory CLL or SLL (AETHER) | • Proportion of U-MRD in BM by NGS and no progression according to iwCLL criteria after 26 cycles (i.e., 12 weeks after cycle 26) for all intent to treat patients • Recommended phase 2 dose for the combination of venetoclax and epcoritamab based on dose limiting toxicity |
| NCT04523428 | REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL) | • U-MRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 acalabrutinib-venetoclax) |
| Clinicaltrials.gov ID . | Study title . | Primary outcomes . |
|---|---|---|
| NCT05478512 | Front-line VenObi Combination Followed by Ven or VenZan Combination in Patients With Residual Disease: a MRD Tailored Treatment for Young Patients With High-risk CLL (VIS) | • U-MRD at month 9 • U-MRD at month 21 |
| NCT04941716 | Acalabrutinib in Combination With Venetoclax for the Treatment of Refractory or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma | • Rate of U-MRD |
| NCT04501939 | Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax | • Percentage of subjects with U-MRD after 6 months of cirmtuzumab and venetoclax treatment |
| NCT04754035 | Clinical Study With Ibrutinib and Venetoclax for Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (IMPROVE) | • U-MRD rate evaluated by multi-color flow cytometry analysis (limit of detection 10−4) within the treatment period |
| NCT05677919 | Pirtobrutinib and Venetoclax Combined With Minimal Residual Disease Detection for Previously Untreated Chronic Lymphocytic Leukemia, MIRACLE Study | • Success of U-MRD (< 1/104) will be measured by ClonoSEQ in both PB and BM; the proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients; exact binomial 95% confidence intervals for the true rate of U-MRD by ClonoSEQ in both PB and BM after cycle 15 will be calculated |
| NCT05650723 | Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab | • Percentage of total patients that have achieved U-MRD at cycle 16, as assessed via PB and BM aspirate • Percentage of eligible patients that have achieved U-MRD at cycle 23, as assessed via PB and BM aspirate |
| NCT05317936 | Pirtobrutinib (LOXO-305) Consolidation for MRD Eradication in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) Treated With Venetoclax | • Rate of U-MRD in the PB |
| NCT05168930 | Zanubrutinib and Venetoclax in CLL (ZANU-VEN) | • Rate of U-MRD |
| NCT03580928 | Acalabrutinib, Venetoclax, and Obinutuzumab for Initial Therapy of CLL (AVO) | • Rate of BM U-MRD complete response |
| NCT04908228 | Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL (FIGHT) | • BM U-MRD (<10−4) at 30 days follow-up |
| NCT02158091 | A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL | • Number of patients who had a U-MRD complete response (CR) 2 months after chemotherapy • Number of patients who experienced a dose limiting toxicity during phase 1 |
| NCT03708003 | Ibrutinib lead-in Followed by Venetoclax Plus Ibrutinib in Patients With RR CLL | • U-MRD CR/CRi at end of cycle 30 |
| NCT04285567 | A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation (CRISTALLO) | • Minimal residual disease (MRD response rate using NGS in the first 140 participants recruited |
| NCT05336812 | Acalabrutinib in Combination With Venetoclax or Obinutuzumab for the Treatment of Treatment-naive Chronic Lymphocytic Leukemia | • Rate of BM U-MRD, defined as tumor cell in 10,000 cells using standard flow-based assay, achieved after completion of therapy |
| NCT04169737 | Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma | • Disease assessment of BM U-MRD (<10−4, MRD4) (TN cohort) • Disease assessment of BM undetectable-MRD4 (RR cohort) |
| NCT04010968 | Evaluation of Risk-Adapted and MRD-Driven Strategy for Untreated Fit Patients With Intermediate Risk Chronic Lymphocytic Leukemia (ERADIC) | • Minimal residual disease (MRD) in BM <0.01% at month 27 |
| NCT05791409 | Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory CLL or SLL (AETHER) | • Proportion of U-MRD in BM by NGS and no progression according to iwCLL criteria after 26 cycles (i.e., 12 weeks after cycle 26) for all intent to treat patients • Recommended phase 2 dose for the combination of venetoclax and epcoritamab based on dose limiting toxicity |
| NCT04523428 | REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL) | • U-MRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 acalabrutinib-venetoclax) |
BM, bone marrow; CRi, incomplete bone marrow recovery; iwCLL, International Workshop on CLL; MRD, measurable residual disease; NGS, next- generation sequencing; Obi, obinutuzumab; PB, peripheral blood; RR, relapsed/refractory; TN, treatment-naive; U-MRD, undetectable MRD; Ven, venetoclax; Zan, zanubrutinib.