Hemoglobinopathies, Coagulation Disorders & Hematologic Malignancies
A comprehensive analysis of the hematology clinical trial landscape — from bone marrow assessment and coagulation laboratory infrastructure to gene therapy administration and pipeline dynamics across sickle cell disease, hemophilia, ITP, and hematologic cancers.
The Hematology Trial Landscape in 2026
Hematology clinical research encompasses a remarkably diverse landscape spanning inherited blood disorders, benign hematologic conditions, and hematologic malignancies. Within the Clinitiative network, hematology represents a strategically important portfolio with 16 active studies across sickle cell disease, hemophilia A and B, immune thrombocytopenia (ITP), beta-thalassemia, lymphoma, leukemia, and multiple myeloma. This breadth reflects both significant unmet need across blood disorders and the transformative innovation in gene therapy, gene editing, bispecific antibodies, CAR-T cell therapy, and novel complement and Fc receptor-targeting mechanisms.
The distribution of active studies reflects the dual nature of hematology research. Hematologic malignancies — lymphoma, leukemia, and multiple myeloma — account for 8 active protocols, driven by bispecific T-cell engagers, next-generation CAR-T therapies, and cereblon-based degrader agents. While these overlap with oncology, they are covered here for blood cancer-specific aspects including stem cell transplant, CAR-T manufacturing, unique hematologic endpoints such as minimal residual disease, and the distinct infrastructure of apheresis and cellular therapy. Sickle cell disease and beta-thalassemia account for 4 gene therapy and gene editing studies, hemophilia A and B represent 2 studies evaluating AAV gene therapy and novel factor mimetics, and ITP and other immune-mediated cytopenias account for 2 studies targeting FcRn inhibition and novel thrombopoietic pathways.
Gene therapy has emerged as the most transformative modality in hematology, with the approvals of exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) for sickle cell disease and beta-thalassemia establishing CRISPR gene editing and lentiviral gene addition as curative approaches. The implications for trial infrastructure are profound: apheresis for stem cell collection, myeloablative conditioning, prolonged hospitalization for engraftment monitoring, and years-long follow-up are now standard protocol elements. Meanwhile, the hematologic malignancy landscape evolves rapidly, with bispecific antibodies and CAR-T therapies demonstrating remarkable efficacy across relapsed and refractory indications.
Key Performance Metrics
Network-wide benchmarks from our hematology portfolio provide critical reference points for study planning, site performance evaluation, and enrollment forecasting across blood disorder indications.
Across all hematology indications, our network sites achieve a median enrollment rate of 1.2 patients per site per month. Hematologic malignancy studies perform above this benchmark at 1.6/mo, benefiting from the large populations of relapsed and refractory patients at comprehensive cancer centers. Hemoglobinopathy studies average 0.8/mo, constrained by geographic concentration of sickle cell and thalassemia populations and gene therapy screening complexity. Hemophilia studies face the greatest challenge at 0.4/mo, reflecting the rare nature of the condition and concentration of eligible patients at specialized hemophilia treatment centers.
Screen failure rates across the hematology portfolio average 26%, moderate compared to other therapeutic areas. Hematologic parameter thresholds including minimum hemoglobin levels, platelet counts, absolute neutrophil counts, and organ function requirements represent the primary barriers. Prior treatment requirements add complexity in malignancy studies where specific prior lines must be documented. Gene therapy studies face unique screen failure drivers including apheresis cell yield adequacy, HLA typing, and organ function thresholds required to tolerate myeloablative conditioning safely.
From contract execution to first patient enrolled, hematology sites achieve a median startup time of 16.2 weeks. This longer timeline reflects complex infrastructure requirements including stem cell transplant and apheresis program certification, gene therapy product handling validation, CAR-T manufacturing logistics coordination, and specialized coagulation laboratory establishment. Sites with established transplant programs and prior gene therapy or CAR-T experience consistently achieve startup 4-5 weeks faster than sites building these capabilities for the first time.
The overall patient retention rate across hematology studies is 86%, reflecting high engagement of patients with chronic blood disorders who view trials as access to potentially curative therapies. Sickle cell disease studies demonstrate particularly strong retention at 90%, driven by the profound unmet need and curative potential of gene therapy. Hematologic malignancy studies show more variable retention at 82%, impacted by disease progression, treatment-related mortality, and the competing option of stem cell transplant. ITP and hemophilia studies maintain retention rates of 88-91%, reflecting the chronic nature of these conditions and motivation to access novel therapies that may reduce bleeding episodes or eliminate chronic treatment requirements.
Network Capabilities
Executing hematology trials at the complexity required by modern protocols demands highly specialized infrastructure, laboratory capabilities, and operational expertise spanning bone marrow biopsy through cellular therapy manufacturing and long-term surveillance. Our network ensures deep hematology-specific capabilities meeting the rigorous demands of gene therapy, coagulation studies, and hematologic malignancy trials.
Bone Marrow Assessment & Flow Cytometry
Bone marrow aspirate and biopsy remain the cornerstone of disease assessment in hematologic malignancies, providing essential data on cellularity, morphology, cytogenetics, and molecular markers for eligibility, response assessment, and MRD status. Our sites maintain dedicated biopsy suites with trained hematopathologists performing posterior iliac crest aspiration and trephine biopsy using standardized techniques for morphologic review, immunohistochemistry, flow cytometry, FISH, and NGS-based molecular profiling. Multiparameter flow cytometry is critical for MRD assessment in leukemia and myeloma, where sensitivity of 10^-4 to 10^-6 is increasingly required. Our sites maintain 8-color or higher platforms with standardized antibody panels validated against EuroFlow standards, and processing within 24 hours ensures timely results.
Coagulation & Hemostasis Laboratory
Hemophilia and coagulation disorder trials require specialized laboratory capabilities far beyond standard coagulation testing. Our sites maintain comprehensive hemostasis laboratories for one-stage and chromogenic factor VIII and IX assays, Bethesda and Nijmegen inhibitor quantification, von Willebrand factor testing, thromboelastography (TEG), rotational thromboelastometry (ROTEM), and platelet function analysis. Strict pre-analytical handling — citrated collection, double centrifugation for platelet-poor plasma, and defined processing windows — ensures accuracy. For gene therapy studies, serial factor activity monitoring over 3-5 years requires assay consistency across timepoints, supported by external quality assessment programs and reference laboratory relationships for confirmatory testing.
Apheresis & Stem Cell Collection
Apheresis capabilities are fundamental to both gene therapy and CAR-T programs. For hemoglobinopathy gene therapy, peripheral blood stem cell collection via leukapheresis following G-CSF and plerixafor mobilization provides starting material for ex vivo gene modification. CAR-T studies require leukapheresis for T-cell collection with specific cell count and viability requirements. Our sites maintain FACT-accredited apheresis programs with dedicated nurses, established mobilization protocols, and standardized cell processing and cryopreservation. CD34-positive cell selection, T-cell subset enumeration, and viability testing are performed on-site or through partnerships. Shipping logistics — validated containers, temperature monitoring, chain-of-custody — are managed by dedicated cellular therapy coordinators throughout the vein-to-vein process.
Transfusion Medicine & Blood Bank
Hematology trials frequently require intensive transfusion support, from chronic red blood cell transfusion in sickle cell disease and thalassemia to platelet thresholds in malignancy studies and myeloablative conditioning support. Our sites maintain comprehensive blood bank services with extended red cell antigen phenotyping for alloimmunized sickle cell patients, irradiated and leukoreduced products, CMV-negative availability, and rare blood type support. Exchange transfusion is particularly important for sickle cell studies requiring pre-treatment hemoglobin S reduction before gene therapy conditioning. Our sites perform both manual and automated exchange procedures with target levels documented per protocol to ensure safe support throughout the peri-transplant period.
Enrollment Dynamics
Hematology enrollment patterns are shaped by the remarkable diversity of conditions within this therapeutic area, ranging from ultra-rare inherited disorders to relatively common hematologic malignancies. Understanding the unique recruitment dynamics of each disease area is essential for realistic enrollment planning and site selection strategies.
Hematologic malignancy recruitment benefits from the established infrastructure of comprehensive cancer centers and community oncology practices, where patients with relapsed or refractory lymphoma, leukemia, and myeloma are frequently evaluated for trial eligibility. The increasingly molecular classification of hematologic malignancies — including specific cytogenetic abnormalities, gene mutations (TP53, MYD88, BRAF), and immunophenotypic markers — means molecular testing results often determine eligibility, requiring sites to have established pathways for rapid molecular profiling.
Sickle cell disease recruitment draws from comprehensive sickle cell centers and community hematology practices serving the predominantly African American patient population. In the United States, approximately 100,000 individuals are affected, with the highest concentrations in the southeastern states, mid-Atlantic region, and major urban centers. Gene therapy recruitment is further constrained by extensive screening requirements, adequate venous access for apheresis, and significant time commitment for conditioning and long-term follow-up. Racial and ethnic diversity is a critical priority, and our network maintains partnerships with sickle cell centers and community organizations that serve as trusted conduits for trial awareness.
Hemophilia recruitment is concentrated at hemophilia treatment centers (HTCs), the primary medical home for most hemophilia patients. With an estimated 20,000 hemophilia A and 4,000 hemophilia B patients nationally, the eligible population is inherently small. Gene therapy studies further narrow eligibility by requiring specific factor activity levels, absence of pre-existing AAV antibodies (excluding 30-50% of patients), and adequate liver function. ITP recruitment benefits from the larger patient population across hematology practices, with established platelet count monitoring providing readily identifiable candidates for novel thrombopoietic agents or FcRn inhibitors.
Key Challenges in Hematology Trial Execution
The extraordinary diversity and complexity of hematology protocols presents operational challenges that require specialized strategies, infrastructure, and deep clinical expertise to address effectively.
Small & Geographically Dispersed Populations
Many hematologic conditions are rare diseases with small, geographically dispersed patient populations that make single-site or regional enrollment strategies insufficient. Hemophilia B affects approximately 4,000 individuals in the United States, and beta-thalassemia major requiring transfusion affects fewer than 2,000. Gene therapy studies targeting these conditions may require national or international multi-site enrollment with 20-30 or more participating sites to achieve targets of 30-50 patients. Our network addresses this through strategic site placement at established hemophilia treatment centers and thalassemia specialty clinics across multiple regions, supplemented by patient identification partnerships with disease-specific registries and advocacy organizations that connect rare disease patients with trial opportunities.
Treatment Landscape Complexity
The hematologic malignancy treatment landscape has become extraordinarily complex, with multiple lines of therapy, numerous approved agents across different drug classes, and evolving definitions of refractory disease that vary between protocols. Eligibility criteria specifying the number and type of prior therapy lines, required exposure to specific drug classes (proteasome inhibitors, immunomodulatory agents, anti-CD38 antibodies in myeloma; BTK inhibitors, PI3K inhibitors in lymphoma), and definitions of treatment failure create significant screening complexity. Coordinators must document prior treatment histories, reconcile differing definitions of treatment lines, and navigate the distinction between relapsed and refractory disease as defined by study-specific criteria. Our network sites employ hematology-specialized coordinators who maintain deep familiarity with the evolving treatment landscape and efficiently pre-screen patients against multiple active protocol eligibility criteria.
Gene Therapy Manufacturing & Logistics
Gene therapy and CAR-T cell therapy involve a complex manufacturing and logistics chain extending far beyond the clinical site. The vein-to-vein time from apheresis collection through manufacturing to product infusion ranges from 4-8 weeks for CAR-T therapies and 12-16 weeks or longer for lentiviral gene therapy products. During manufacturing, patients must be managed to maintain eligibility, which may include bridging therapy for malignancy patients or continued transfusion support for hemoglobinopathy patients. Manufacturing failures, occurring in 5-10% of cases, represent a significant operational and ethical challenge, as patients who have undergone apheresis and possibly conditioning may not receive treatment. Our sites maintain contingency protocols including pre-defined bridging therapy options, alternative study pathways, and transparent communication plans for patients navigating this uncertainty.
Health Equity in Sickle Cell Research
Sickle cell disease disproportionately affects Black and African American individuals, a population historically underrepresented in clinical research that faces significant barriers to trial participation including medical mistrust rooted in events such as the Tuskegee Study, geographic distance from academic medical centers, socioeconomic barriers including transportation costs and time away from work, and insurance-related access barriers for gene therapy conditioning and follow-up. Our network addresses these equity challenges through intentional site placement at institutions serving diverse communities, community engagement programs with sickle cell advocacy organizations, culturally competent informed consent processes, and practical support including transportation assistance, childcare coordination, and flexible scheduling that reduce the burden of participation.
Pipeline Analysis
The hematology development pipeline is among the most innovative in medicine, with gene therapy, gene editing, bispecific antibodies, and novel targeted agents driving transformative shifts in how blood disorders are treated. Several modalities are reshaping trial design, site requirements, and enrollment strategies across hematologic indications.
Gene Therapy for Hemoglobinopathies
The approval of lentiviral gene addition (lovotibeglogene autotemcel) and CRISPR gene editing (exagamglogene autotemcel) for sickle cell disease and beta-thalassemia has established gene therapy as a curative option for hemoglobinopathies. The next wave focuses on improving safety, accessibility, and scalability. Non-myeloablative conditioning avoiding busulfan is being evaluated to reduce toxicity and enable treatment of patients excluded due to organ damage. In vivo gene therapy delivering editing machinery directly — without apheresis, ex vivo manufacturing, or myeloablative conditioning — could dramatically expand access. Additional editing targets beyond BCL11A, including direct sickle mutation correction and fetal hemoglobin regulatory element reactivation, are in preclinical and early clinical development.
Next-Generation Hemophilia Therapies
Hemophilia treatment is shifting from chronic factor replacement toward curative gene therapy and non-replacement strategies. AAV-based gene therapy for hemophilia A (AAV5 vectors carrying factor VIII transgenes) and hemophilia B (AAV vectors carrying factor IX Padua variants) has demonstrated durable factor activity expression, with some patients maintaining therapeutic levels for 5+ years. Challenges remain including variable expression over time, pre-existing AAV antibodies that exclude a significant proportion of patients, and liver enzyme elevations requiring immunosuppression. The next generation includes novel capsid engineering to evade pre-existing immunity, alternative tissue targeting, and higher-potency transgene constructs. Bispecific antibodies mimicking factor VIII function (building on the emicizumab paradigm) and RNA interference-based approaches targeting antithrombin (fitusiran class) provide non-replacement alternatives for ineligible patients.
Novel Agents for Hematologic Malignancies
The hematologic malignancy pipeline is defined by the convergence of innovative modalities. Bispecific T-cell engagers — antibodies binding tumor antigens (CD20, BCMA, GPRC5D, FcRH5) and CD3 on T cells — are demonstrating remarkable response rates in relapsed/refractory lymphoma and myeloma, rapidly advancing into earlier therapy lines. Next-generation CAR-T therapies targeting novel antigens and exploring allogeneic (off-the-shelf) platforms that eliminate patient-specific manufacturing are progressing through development. Cereblon E3 ligase modulators (CELMoDs) represent next-generation targeted protein degradation in myeloma and lymphoma. These studies require cytokine release syndrome and ICANS management infrastructure, intensive post-infusion monitoring, and MRD assessment at unprecedented sensitivity levels.
Complement & Immune-Mediated Hematology
Complement-mediated and immune-mediated blood disorders represent a growing area of hematology development. Complement inhibitors targeting C5 (eculizumab, ravulizumab), factor B (iptacopan), and factor D (danicopan) have transformed treatment of PNH and aHUS, and next-generation oral complement inhibitors aim to replace injectable therapies. In ITP, FcRn inhibitors (rozanolixizumab, nipocalimab) reduce pathogenic IgG autoantibody levels by accelerating IgG catabolism, providing an alternative to thrombopoietin receptor agonists and splenectomy. Novel thrombopoietic agents with improved dosing convenience are also in development. These studies require specialized complement laboratory assessments, infection risk monitoring, and platelet count infrastructure for dose-adjustment protocols.
Site Requirements for Hematology Excellence
The infrastructure, staffing, and operational processes required to execute modern hematology protocols at the highest level of laboratory precision, patient safety, and regulatory compliance.
Dedicated bone marrow biopsy procedure area with trained hematopathologists, standardized posterior iliac crest aspiration and trephine biopsy techniques, specimen processing for morphology, immunohistochemistry, flow cytometry, FISH, and NGS-based molecular profiling. Adequate specimen collection for both local and central pathology review requirements.
Comprehensive hemostasis laboratory with one-stage and chromogenic factor assays, Bethesda/Nijmegen inhibitor testing, thromboelastography, von Willebrand factor panel, and platelet function analysis. External quality assessment program participation, standardized pre-analytical handling, and established reference laboratory relationships for confirmatory testing.
FACT-accredited or equivalent apheresis program with dedicated apheresis nurses, leukapheresis and stem cell collection capabilities, CD34-positive cell enumeration, cell viability testing, cryopreservation infrastructure, and validated shipping protocols for cellular products to centralized manufacturing facilities. Mobilization protocol management and contingency procedures for poor mobilizers.
Comprehensive blood bank with extended red blood cell antigen phenotyping, irradiated and leukoreduced product availability, CMV-negative product access, rare blood type support, and automated red blood cell exchange capability for sickle cell disease protocols. 24/7 transfusion support during conditioning and engraftment periods for gene therapy studies.
Research pharmacy with hazardous drug handling capabilities for myeloablative conditioning agents (busulfan, cyclophosphamide), cryogenic storage for gene therapy and CAR-T cell products, investigational product chain-of-custody documentation, and pharmacist expertise in biologic and cellular therapy product preparation, thawing protocols, and viability verification prior to patient administration.
Dedicated hematology clinical research coordinators with disease-specific training across malignancies and benign hematology, transplant-certified research nurses experienced in conditioning regimen administration and CRS/ICANS management, cellular therapy coordinators managing the vein-to-vein logistics chain, and regulatory coordinators handling the complex multi-committee review processes required for gene therapy and cellular therapy protocols.
Discuss Your Hematology Program
Connect with our team to explore site capabilities, enrollment strategies, and specialized infrastructure for your hematology clinical development program.