Experimental Drug for Leukemia Post-Stem Cell Transplant

Recruiting at 14 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: TScan Therapeutics, Inc.

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a multi-center, non-randomized, concurrent controlled, multi-arm, Phase 1 interventional, open-label, biologic assignment-based umbrella study evaluating the feasibility, safety and preliminary efficacy of an escalating dose regimen of up to 2 doses of TSC-100 and TSC-101 in patients with AML, MDS, or ALL following HCT from a haploidentical donor.

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.

What data supports the effectiveness of the treatment TSC-100 and TSC-101 for leukemia post-stem cell transplant?

Research on timed sequential chemotherapy (TSC) shows that it can lead to higher rates of complete remission and improved long-term outcomes in patients with acute myelogenous leukemia, suggesting potential benefits for similar treatments like TSC-100 and TSC-101. ^{1 2 3 4 5}

Is the experimental drug for leukemia post-stem cell transplant safe?

The research suggests that peripheral blood stem cell transplantation (PBSCT) is generally safe for treating various conditions, including leukemia, but there can be risks like graft-versus-host disease (GVHD) and complications such as neutropenic enterocolitis (a serious bowel condition). ^{6 7 8 9 10}

What makes the experimental drug for leukemia post-stem cell transplant unique?

The experimental drug TSC-100 and TSC-101 for leukemia post-stem cell transplant is unique because it is being tested specifically for use after stem cell transplants, which is a novel approach compared to standard treatments that typically do not focus on this post-transplant phase. This trial may offer new insights into preventing relapse and improving outcomes in patients who have undergone stem cell transplants for leukemia. ^{3 9 11 12 13}

Research Team

Shrikanta Chattopadhyay, MD

Principal Investigator

Tscan Therapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Control (Other)
• TSC-100 (Other)
• TSC-101 (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States 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. [2017]

3. China 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]. [2018]

4. United States 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. [2013]

5. China 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]. [2010]

6. England 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. [2006]

7. Japan pubmed.ncbi.nlm.nih.gov

[Peripheral blood stem cell transplants: clinical considerations and observations in practice in a general hospital]. [2007]

8. China pubmed.ncbi.nlm.nih.gov

[Comparison of clinical outcomes between unrelated donor peripheral blood stem cell transplantation and bone marrow transplantation for leukemia]. [2006]

9. United States 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. [2017]

10. Japan pubmed.ncbi.nlm.nih.gov

[A case of neutropenic enterocolitis in high dose chemotherapy with peripheral blood stem cell transplantation for relapsed testicular tumor]. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Successful autograft with peripheral blood stem cells in a child with T-lymphoblastic leukemia. [2019]

12. China pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors. [2007]

13. England 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. [2007]