5 Ongoing Phase 3 Trials in Hematologic Malignancies

Each of these ongoing phase 3 trials in a hematologic malignancy is aiming to optimize frontline therapies and improve long-term patient outcomes. These studies focus on outcomes among adult patients with chronic lymphocytic leukemia (CLL), multiple myeloma, or small lymphocytic leukemia (SLL), and pediatric/adolescent/young adult patients with acute leukemia or myelodysplastic syndrome (MDS). The patient populations encompass patients who are newly diagnosed, treatment naïve, and considered high risk. All of the trials are international, randomized, open-label investigations, with estimated primary completion dates between June 2026 and June 2033.^1-5

Chronic Lymphocytic Leukemia

The 652 treatment-naïve patients enrolled in this trial (NCT06073821)¹ receive the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib with the BCL-2 inhibitor sonrotoclax, both oral administrations, or the BCL-2 inhibitor venetoclax with anti-CD20 monoclonal antibody obinutuzumab, oral and intravenous administration, respectively. The primary outcomes of interest are progression-free survival (PFS) up to 9 years and rate of undetectable minimal residual disease (MRD) up to 1.5 years, and secondary outcomes include complete response (CR), overall survival (OS), undetectable MRD, and duration of response, all up to 9 years. Treatment cycles in both arms are 28 days. To participate, all patients had to have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 through 2, confirmed measurable disease via CT or MRI, and adequate liver and renal function. Uncontrolled hypertension, central nervous system involvement, and previous systemic treatment precluded participation. The current estimated date of final data collection for the primary outcome measures is February 2032.

Multiple Myeloma

The CARTITUDE-6 trial (NCT05257083)² is comparing the quadruplet chemotherapy regimen of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) plus DVRd and chimeric antigen receptor T-cell therapy (ciltacabtagene autoleucel) vs DVRd and autologous stem cell transplant in patients with newly diagnosed disease who are eligible for transplant (N = 759). The primary outcomes of interest are PFS up to 10 years or 300 PFS events and sustained MRD-negativity CR up to 24 months. Secondary outcomes include overall response, CR or better, overall MRD-negative CR, and OS, all up to 17 years. Inclusion criteria include newly diagnosed disease per International Myeloma Working Group criteria and ECOG PS of grade 0 or 1. Exclusion criteria include stroke or seizure in the 6 months prior to study consent and history of CAR T-cell therapy for any target.

CLL or Small Lymphocytic Leukemia

In the MAJIC trial (NCT05057494),³ outcomes are being evaluated between patients receiving venetoclax and obinutuzumab or venetoclax and the BTK inhibitor acalabrutinib. The total enrollment is 607 adult patients who are 18 years and older with documented treatment-naïve CLL or SLL, adequate bone marrow function as measured by absolute neutrophil count of at least 1.0 × 10⁹/L without bone marrow involvement or at least 0.50 × 10⁹/L with bone marrow involvement and respective platelet counts of at least 30 × 10⁹/L or at least 10 × 10⁹/L, and estimated creatinine clearance of 30 mL/min or more (using body weight) or less than 2 × upper limit of normal. Exclusion criteria include significant comorbidities (eg, cardiovascular disease, cerebrovascular disease, active bleeding, malignancy history), organ system dysfunction, and current HIV infection or any significant infection. The primary outcome of interest is PFS, measured up to 6.6 years, and secondary outcomes include undetectable MRD in the peripheral blood, OS up to 6.6 years, event-free survival (EFS), and change from baseline score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire.

Pediatric Acute Lymphoblastic Leukemia

The most common cancer diagnosed in children, acute lymphoblastic leukemia (ALL) has an approximate 5-year survival rate of 90% following diagnosis, with prominent prognostic factors being age at diagnosis and initial white blood cell count.⁴ In this trial sponsored by Dana-Farber Cancer Institute (NCT06073821),⁵ pegaspargase, an antineoplastic chemotherapy, is being evaluated in 3 arms: randomized 2500 IU/m² every 2 weeks (the standard/fixed-dose arm), randomized 2000 IU/m² starting dose (reduced-dose arm), and directly assigned 2500 IU/m² if considered very high risk or the patient declined randomization. Investigators will also use new and updated risk factors concurrent with old risk factors to ultimately determine treatment strength. Patients allergic to pegaspargase or who show silent inactivation will instead receive erwinia asparaginase. The primary outcomes to be measured are complete remission rate and EFS, and secondary outcomes of interest are OS, disease-free survival, nadir serum asparaginase activity, and nonallergic asparaginase toxicity.

Pediatric MDS/Acute Leukemia

In the setting of stem cell transplantation, the authors of this study (NCT05457556)⁶ want to know if cells from a matched unrelated donor (MUD) or cells from a haplo-related donor (a 50% genetic match to the patient⁷) produce superior outcomes vs the other, or if the 2 methods are equally effective. Participants are randomly assigned to haplo hematopoietic (stem) cell transplantation (HCT) or to an 8/8 adult MUD-HCT. The primary objective is a 1-year cumulative incidence of severe graft versus host disease (GVHD) or chronic GVHD in children and young adults who have any of the following: acute myeloid leukemia, ALL, mixed phenotype acute leukemia, or MDS. Secondary outcomes of interest are OS and health-related quality of life at 6 months, 1 year, and 2 years after transplant compared with baseline. Exploratory objectives include median time to engraftment; 1 year, 18-month, and 2-year cumulative incidence of GVHD-free relapse-free survival; and immune recovery after posttransplant cyclophosphamide, haplo alpha-beta T cell depletion, and MUD HCT.

References

1. Study of sonrotoclax (BGB-11417) plus zanubrutinib (BGB-3111) compared with venetoclax plus obinutuzumab in participants with chronic lymphocytic leukemia (CLL). ClinicalTrials.gov. Updated January 22, 2026. Accessed January 25, 2026. https://clinicaltrials.gov/study/NCT06073821
2. A study of daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) followed by ciltacabtagene autoleucel versus daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) followed by autologous stem cell transplant (ASCT) in participants with newly diagnosed multiple myeloma (CARTITUDE-6). ClinicalTrials.gov. Updated December 18, 2025. Accessed January 25, 2026. https://clinicaltrials.gov/study/NCT05257083
3. A study of acalabrutinib plus venetoclax versus venetoclax plus obinutuzumab in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (MAJIC). ClinicalTrials.gov. Updated November 17, 2025. Accessed January 25, 2026. https://clinicaltrials.gov/study/NCT05057494
4. Prognostic factors and survival rates for childhood leukemia. American Cancer Society. Revised July 22, 2025. Accessed January 25, 2026. https://www.cancer.org/cancer/types/leukemia-in-children/detection-diagnosis-staging/survival-rates.html
5. Treatment of newly diagnosed acute lymphoblastic leukemia in children and adolescents. ClinicalTrials.gov. Updated January 22, 2026. Accessed January 25, 2026. https://clinicaltrials.gov/study/NCT06073821
6. Mismatched related donor versus matched unrelated donor stem cell transplantation for children, adolescents, and young adults with acute leukemia or myelodysplastic syndrome. ClinicalTrials.gov. Updated December 22, 2025. Accessed January 25, 2026. https://clinicaltrials.gov/study/NCT05457556
7. What is a haploidentical blood or marrow transplant? National Marrow Donor Program. Accessed January 25, 2026. https://www.nmdp.org/patients/understanding-transplant/haploidentical-transplant