Experimental Drug for Leukemia Post-Stem Cell Transplant

Recruiting at 14 trial locations

Overseen By Sameem M. Abedin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TScan Therapeutics, Inc.

Disqualifiers: Active cardiac disease, Significant infection, Prior HCT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with certain types of leukemia who have received a stem cell transplant from a partially matched donor. It tests the safety and effectiveness of two experimental drugs, TSC-100 and TSC-101, to determine if they can improve outcomes post-transplant. Participants include those with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphoblastic leukemia (ALL) who have already undergone or are preparing for a stem cell transplant from a partially matched donor. Individuals with specific genetic markers related to their immune system may qualify for one of the two treatment arms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive these new drugs.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TSC-100 and TSC-101 are being tested for safety in patients after a stem cell transplant. The main goal of these studies is to identify any adverse reactions or side effects when these drugs are administered, either once or multiple times.

Early results suggest that TSC-100 and TSC-101 might help reduce the risk of cancer recurrence after treatment. However, as this is an early-stage study, researchers are still gathering safety information. Early trials often focus on ensuring the treatment does not cause harm and is generally well-tolerated. Much remains to be learned about the long-term effectiveness and safety of these treatments.

In summary, while TSC-100 and TSC-101 show promise, the current phase of trials primarily focuses on assessing safety and observing patient reactions to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TSC-100 and TSC-101 because they offer a new way to target leukemia cells after a stem cell transplant. Unlike traditional treatments that mainly rely on chemotherapy and radiation, these therapies are designed to be more precise. TSC-100 targets HA-1 positive patients, while TSC-101 focuses on HA-1 negative and HA-2 positive patients, using the unique markers on leukemia cells to distinguish and attack them. This specificity could lead to fewer side effects and a more personalized approach, potentially improving outcomes for patients who have undergone a stem cell transplant.

What evidence suggests that this trial's treatments could be effective for leukemia post-stem cell transplant?

This trial will evaluate the effectiveness of TSC-100 and TSC-101 as separate treatments to reduce the chances of leukemia returning after a stem cell transplant. Participants may receive either TSC-100 or TSC-101, which target and eliminate leftover cancer cells, potentially lowering the risk of recurrence. Early results suggest these treatments can help patients remain cancer-free longer. Research indicates that TSC-100 and TSC-101 might be effective for conditions like acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS). Although more research is needed, early data show promising signs that these treatments could benefit patients who have had transplants. ^{1 2 3 5 6}

Who Is on the Research Team?

Michelle Matzko, MD

Principal Investigator

Tscan Therapeutics

Are You a Good Fit for This Trial?

Adults (≥18 years) with AML, ALL, or MDS preparing for haploidentical donor transplantation. They must have specific HLA types and genotypes (HA1+/- or HA-1+/+ for TSC-100; HA2+/- or HA-2+/+ for TSC-101), good organ function, and an ECOG performance status ≤ 2. Contraception is required during the study and up to a year after. Exclusions include unsuitability for cell therapy, certain heart conditions, hypersensitivity to murine proteins, high levels of donor-specific HLA antibodies without alternative donors.

Inclusion Criteria

My organs are healthy enough for a transplant according to hospital rules.

I am preparing for a stem cell transplant for my leukemia or MDS.

Capable of giving signed informed consent and agreeing to comply with study procedures and restrictions

Exclusion Criteria

Medical or psychological conditions that would make the participant an unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)

I am HLAA*02:07 positive and meet the criteria for TSC-101.

My doctor may delay my treatment if I have organ problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TSC-100 or TSC-101 combined with standard of care, including reduced intensity conditioning and hematopoietic cell infusion

6 months

Multiple visits for dose administration and monitoring

Dose Escalation

Successive cohorts receive escalating doses of TSC-100 or TSC-101, with safety reviews after each cohort

40 days per cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and survival

2 years

Regular follow-up visits for safety and efficacy assessments

What Are the Treatments Tested in This Trial?

Interventions

• Control
• TSC-100
• TSC-101

Trial Overview The trial tests two treatments: SOC + TSC-100 and SOC + TSC-101 against a control group in patients undergoing stem cell transplantation from a half-matched donor. It's open-label with multiple arms assessing safety, feasibility, and preliminary effectiveness of escalating doses of these therapies.

How Is the Trial Designed?

Group I: TSC-100 Treatment Arm Experimental Treatment 1 Intervention

HA-1 positive patients

Group II: TSC 101 Treatment Arm Experimental Treatment 1 Intervention

HA-1 negative and HA-2 positive patients

Group III: Standard of Care or Control arm Active Control 1 Intervention

Who Is Running the Clinical Trial?

TScan Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,400+

Published Research Related to This Trial

Timed sequential chemotherapy (TSC) has been shown to increase complete remission rates in adults with acute myelogenous leukemia, which is crucial for improving long-term survival outcomes.

The strategy of TSC takes advantage of the synchronized recruitment of leukemic cells into the cell cycle after initial treatment, making them more vulnerable to chemotherapy, thus enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of timed sequential chemotherapy in adult acute myelogenous leukemia. Thomas, X.[2021]

In a study of 133 patients with previously treated acute myelogenous leukemia (AML), 60% achieved complete remission (CR) with a specific chemotherapy regimen, indicating significant efficacy, especially in late first-relapse patients (76% CR).

However, the treatment was associated with considerable toxicity, including severe nonhematologic side effects like sepsis (54% of patients) and a median survival of only 7 months for those not undergoing transplantation, highlighting the need for careful management of treatment-related risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial. Archimbaud, E., Thomas, X., Leblond, V., et al.[2017]

The study involved 18 patients with small cell lung cancer (SCLC) who underwent double-cycle, high-dose chemotherapy followed by peripheral blood stem-cell transplantation (PBSCT), demonstrating that this treatment approach is tolerable and feasible after conventional chemotherapy.

The treatment resulted in a 100% overall response rate, with 83.3% achieving a complete or near-complete response, and notable 2-year survival rates of 72% for patients with limited disease, indicating significant efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-cycle, high-dose ifosfamide, carboplatin, and etoposide followed by peripheral blood stem-cell transplantation for small cell lung cancer. Iwasaki, Y., Nagata, K., Nakanishi, M., et al.[2013]

In a study involving 20 patients with small cell lung cancer (SCLC), high dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT) showed promising results, particularly in patients who achieved complete remission (CR), with some surviving over 4 years after treatment.

While the treatment was feasible and safe for those in CR, the side effects were severe, and patients receiving salvaging therapy had a shorter median remission time of only 3.5 months, indicating the need for further research in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT) in the treatment of patients with small cell lung cancer]. Bao, Y., Su, H., Shen, G., et al.[2010]

In a multicenter phase II study involving 22 patients with standard-risk leukemia, allogeneic peripheral blood stem cell transplantation (allo-PBSCT) resulted in rapid recovery of blood cell counts, with a median of 12 days to achieve neutrophil counts over 500/microl and 16 days for platelet counts over 50,000/microl.

While allo-PBSCT showed no increase in the incidence of acute graft-versus-host disease (GVHD), there was a notable risk of chronic GVHD, affecting 60% of patients, suggesting that while this method is effective, careful monitoring for chronic GVHD is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation for standard-risk leukemia. A multicenter pilot study: Japanese experience. Japan Blood Cell Transplantation Study Group. Harada, M., Shinagawa, K., Kawano, T., et al.[2006]

Donor peripheral blood stem cell (PBSC) infusion, mobilized by granulocyte colony-stimulating factor (G-CSF), is effective and safe for preventing relapse in leukemia patients after haploidentical hematopoietic stem cell transplantation (HSCT), with a 2-year disease-free survival rate of 52.5%.

Among the 20 patients treated, 22.9% experienced acute graft-versus-host disease (GVHD), but no deaths were attributed to GVHD, indicating that while some patients faced complications, the overall treatment was manageable and did not lead to increased mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effects of donor peripheral blood stem cell infusion in the prevention of relapse in high risk leukemia after haplotype hematopoietic stem cell transplantation]. Zhang, Y., Chen, HR., Liu, XD., et al.[2018]

Autologous peripheral blood stem cell transplantation (auto-PBSCT) significantly improves long-term survival rates in patients with hematological tumors, with 3-year survival rates of 83.3% for non-Hodgkin lymphoma (NHL) and 74.7% for acute myeloid leukemia (AML).

The use of granulocyte colony stimulating factor (G-CSF) after auto-PBSCT accelerates neutrophil recovery, reducing the average recovery time from 17.6 days to 11.14 days, while the procedure is associated with manageable complications and no transplantation-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors. Ke, X., Yang, Y., Zhao, X., et al.[2007]

In a study of 35 patients with acute myeloid leukemia (AML) in first complete remission, peripheral blood stem cells (PBSC) collected after G-CSF priming were successfully used for autologous transplantation, with no transplant-related mortality reported.

Early intensification therapy before PBSC collection significantly improved disease-free survival rates, with a 68.8% probability of remaining disease-free compared to 35.5% for those who did not receive this therapy, indicating its effectiveness in reducing relapse risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome. Martín, C., Torres, A., León, A., et al.[2007]

Patients receiving G-CSF mobilized peripheral blood stem cell (PBSC) transplants experienced significantly faster engraftment of neutrophils and platelets compared to those receiving bone marrow (BM) transplants, with times of 12.43 days and 14.67 days for PBSCs versus 16.16 days and 21.23 days for BMs, respectively.

Despite the faster engraftment with PBSCs, there were no significant differences in T cell reconstitution, infection rates, graft-versus-host disease (GVHD) incidences, or 2-year disease-free survival rates between the PBSC and BM transplant groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of clinical outcomes between unrelated donor peripheral blood stem cell transplantation and bone marrow transplantation for leukemia]. Fan, ZP., Yang, K., Liu, QF., et al.[2006]

High dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT) is a safe and effective treatment for refractory or relapsed testicular tumors, as indicated by its use in clinical cases.

However, this treatment can lead to serious complications, such as neutropenic enterocolitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of neutropenic enterocolitis in high dose chemotherapy with peripheral blood stem cell transplantation for relapsed testicular tumor]. Muraki, O., Itoh, M., Haga, N., et al.[2013]

A 3-year-old girl with T-lymphoblastic leukemia successfully underwent a peripheral blood stem cell (PBSC) autograft after failing first-line treatment, leading to her complete remission 47 months post-procedure.

The PBSC autograft demonstrated effective recovery of blood cell counts, with granulocytes and platelets reaching safe levels shortly after infusion, suggesting it can be a viable alternative to traditional bone marrow transplantation for certain pediatric leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful autograft with peripheral blood stem cells in a child with T-lymphoblastic leukemia. Abe, T., Koyama, T., Takaue, Y., et al.[2019]

Peripheral blood stem cell transplants (PBSCTs) are shown to be a safe and effective treatment for patients with malignant tumors after high-dose chemotherapy, with successful outcomes recorded in a study of 36 patients.

Patients with acute lymphocytic leukemia had a 100% disease-free survival rate for an average of 11.3 months, while those with acute non-lymphocytic leukemia had a 60% disease-free survival rate for an average of 12.8 months, indicating varying outcomes based on leukemia type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peripheral blood stem cell transplants: clinical considerations and observations in practice in a general hospital]. Ohta, T., Kishida, T., Hasegawa, T., et al.[2007]

In a study of 24 AML patients undergoing autologous blood stem-cell transplantation (ABSCT), the procedure demonstrated quick recovery of blood cell counts, with most patients achieving necessary levels within 19 days, indicating its efficacy and safety as a treatment option.

While ABSCT showed promising results with a 35% disease-free survival rate at 30 months, there were still challenges with relapse, as 12 patients experienced relapse within 9 months, highlighting the need for further strategies to prevent this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution. Sanz, MA., de la Rubia, J., Sanz, GF., et al.[2017]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/924/530883/TSC-100-and-TSC-101-Demonstrate-the-Potential-to

TSC-100 and TSC-101 Demonstrate the Potential to Reduce ... TSC-100 and TSC-101 demonstrate the potential to reduce relapse rates and increase relapse-free survival in patients with AML, ALL, or MDS undergoing ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2678

A phase 1 trial of TSC-100 and TSC-101, engineered T cell ... TSC-100 or TSC-101 can potentially eliminate all residual patient-derived hematopoietic cells after HCT, to prevent disease relapse.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05473910

NCT05473910 | A Study of TSC-100 and TSC-101 in AML, ... The primary objective of this study is to investigate the safety of single and repeated dosing of TSC-100 and TSC-101 in HLA A*02:01 positive patients ...

4. onclive.com onclive.com/view/dr-al-malki-on-the-potential-use-of-tsc-100-and-tsc-101-after-transplant-in-aml-all-and-mds

Dr Al Malki on the Potential Use of TSC-100 and TSC-101 ... Al Malki, MD, discusses the potential use of TSC-100 and TSC-101 following allogeneic stem cell transplant in patients with AML, ALL or MDS.

5. synapse.patsnap.com synapse.patsnap.com/article/harnessing-tsc-100-unleashing-the-power-of-natural-ha-1-specific-tcrs-in-post-transplant-leukemia-therapy

Harnessing TSC-100: Unleashing the Power of Natural HA ... A significant portion of AML patients experience relapse after hematopoietic stem cell transplant, necessitating new treatment strategies.

6. jitc.bmj.com jitc.bmj.com/content/8/Suppl_3/A94

156 Discovery of TSC-100: A natural HA-1-specific TCR to ... Background Approximately 30–40% of AML patients relapse following allogeneic hematopoietic stem cell transplant therapy, leaving them with very ...