Clinical Research Directory

Leukemia Adapted Protocol

In resource-constrained settings such as Malawi, survival rates for pediatric acute myeloid leukemia (AML) are dismally low compared to high-resource environments. This disparity highlights the urgent need for feasible treatment protocols tailored to the realities of these regions where most children with cancer are treated. In 2023, after reviewing favorable clinical trials results in other resource-limited settings, the Kamuzu Central Hospital (KCH) pediatric cancer unit adopted an evidence-based intensity-adapted clinical practice guideline (CPG) developed by the International Society of Paediatric Oncology (SIOP) as its standard of care for the treatment of pediatric AML, aiming to balance curative intent with manageable toxicity. The current study is a prospective evaluation of outcomes of standard of care in Malawi using the SIOP CPG in a real-world setting. The LEAP study aims to assess the implementation of the SIOP AML guidelines at KCH in an effort to continually improve outcomes in Malawi. The study is an observational-implementation design with a composite effectiveness-implementation outcome called Implementation Success. Implementation Success combines feasibility, the ability of patients to complete all aspects of the CPG, with effectiveness, the ability to maintain historical rates of complete remission of 40% at the treatment center. This prospective cohort study will enroll children under 18 years diagnosed with de novo AML at KCH. Implementation Success will be the primary endpoint, with secondary endpoints including CPG fidelity, long-term survival, adverse events, and hematologic recovery times. Patient-reported outcomes will also be collected to assess the impact of treatment on quality of life. This will be the first prospective study of pediatric AML in sub-Saharan Africa, providing critical data on the management of AML in low-resource settings. By assessing the implementation of a context-adapted CPG, the study will contribute to the global effort to improve pediatric AML outcomes in resource-constrained environments. The findings will serve to guide practitioners in Malawi and similar settings, and the data generated will be invaluable for future clinical decisions and CPG development.

Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression

The purpose of this study is to understand the safety, tolerability, efficacy, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of orally administered AZD3632 in participants with advanced haematologic malignancies with KMT2Ar, NPM1m, or other genotypes associated with homeobox (HOX) overexpression.

Clinical Study of U32 in Patients With Acute Myeloid Leukemia

This is a single-arm, open-label clinical study to evaluate the safety, tolerability, and efficacy of U32 injection in patients with acute myeloid leukemia.

Vaccination Against Human Papillomavirus (HPV) After Allogeneic Stem Cell Transplantation

Patients who undergo allogeneic stem cell transplantation lose previously acquired immunity and are routinely revaccinated against many infectious diseases. For several reasons, these patients have a long-term immune deficiency due to the transplant itself (lack of immune reconstitution) and due to possible complications, primarily GvHD and its treatment. The risk of secondary malignancy in the long-term following an allogeneic bone marrow transplant is greatly increased, and secondary cancer cases account for a significant proportion of late deaths in both women and men after transplantation. Some of these secondary cancers are associated with HPV. The risk of cervical cancer has been reported to be 13 times increased compared to a healthy population. Therefore in this trial, the aim is to study immune response (antigen-specific antibody response) after vaccination with 9-valent HPV vaccine (Gardasil 9®) in adult women and men (up to and including 45 years of age) who have undergone allogeneic stem cell transplantation. In this trial, the sponsor will compare "early" (start 9 months after tx) with "late" (start 15 months after tx) vaccination.

Anti-NKG2A Monoclonal Antibody for AML or MDS Patients Undergoing Haploidentical Transplantation

The goal of this clinical trial is to evaluate the effectiveness and safety of the anti-NKG2A monoclonal antibody (Monalizumab) in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The main questions this trial aims to answer are: * Does Monalizumab improve graft-versus-host disease-free and progression-free survival (GPFS) in patients after Haplo-SCT? * What are the safety and side effects of Monalizumab in this patient group? * How does Monalizumab affect the reconstitution and function of NK cells in patients undergoing Haplo-SCT? * Researchers will administer Monalizumab to participants on day +30 and +44 after transplantation to see if it enhances immune responses and prevents disease relapse or GVHD. Participants will: * Receive Monalizumab intravenously at 1 mg/kg on day +30 and day +44 after Haplo-SCT * Be monitored for clinical outcomes such as GVHD, survival rates, and immune function for up to one year after the transplant * Undergo regular checkups and tests to assess the effectiveness and safety of the treatment

Effectiveness of Early Intervention in Palliative Care for Acute Myeloid Leukemia Patients Comparing to Standard of Care

Hemato-oncology patients undergoing intensive chemotherapy treatments experience different types of symptoms during and after treatments, which are often refractory to the established therapy. Physical symptoms such as pain, dyspnea, mucositis, insomnia, loss of appetite, constipation and diarrhea, among others, have a huge impact on quality of life, temporarily until symptomatic control, but also permanently with the development of anxiety, depression, long-term fatigue and post-traumatic stress. As recommended by ASCO (American Society of Clinical Oncology), the palliative approach to oncological diseases must be as early as possible and be part of the "standard of care". However, the lack of concrete data on this topic in the last decade served as a barrier to the early integration of this same care for hemato-oncology patients in its various areas. Palliative care presupposes global, interdisciplinary action, carried out by specific teams that must act in situations of incurable or serious illness, in an advanced and progressive phase. The potential benefits can be countless and of significant importance, from the impact on quality of life, symptomatic control, reduction of anxiety and depression and even the promotion of informed and conscious choices at the end of life as well as the reduction of aggressive strategies. used at this stage of the disease.

MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)

Investigator proposed to apply the new dosage form of mitoxantrone hydrochloride liposomes to the clinical treatment of AML, while combining with cytarabine and azacitidine to form the MA+AZA treatment regimen(Mitoxantrone liposome +Ara-Cytarabine+Azacitidine), which would provide an optimal induction treatment regimen for patients with primary AML by comparing with the traditional chemotherapy regimen, DA+AZA (Daunorubicin+Ara-Cytarabine+Azacitidine).

International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia

The main purpose of this study is : 1. To establish which number of doses of gemtuzumab ozogamicin (up to a maximum of 3 doses) is tolerated and can be safety delivered in combination with cytarabine plus mitoxantrone or liposomal daunorubicin in induction 2. To compare mitoxantrone (anthracenedione) \& cytarabine with liposomal daunorubicin (anthracycline) \& cytarabine as induction therapy. (Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug.) 3. To compare a single dose of gemtuzumab ozogamicin with the optimum tolerated number of doses of gemtuzumab ozogamicin (identified by the dose-finding study) when combined with induction chemotherapy. 4. To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine \& cytarabine (FLA) in standard risk patients. 5. To compare the toxicity and effectiveness of two haemopoietic stem cell transplant (HSCT) conditioning regimens of different intensity: conventional myeloablative conditioning (MAC) with busulfan/cyclophosphamide and reduced intensity conditioning (RIC) with fludarabine/busulfan.