Iomab-B + HCT for Acute Myeloid Leukemia

(SIERRA Trial)

Recruiting at 23 trial locations

Overseen By Vijay Reddy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Actinium Pharmaceuticals

Must not be taking: Investigational agents

Disqualifiers: CNS involvement, Cardiac disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

153 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).

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

The trial information does not specify if you need to stop taking your current medications. However, it allows the use of hydroxyurea to control blast count, which suggests some medications might be allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Iomab-B + HCT for Acute Myeloid Leukemia?

Research shows that allogeneic hematopoietic stem cell transplantation (AHSCT) can be effective for patients with acute myeloid leukemia (AML) who do not respond to initial chemotherapy, suggesting that combining it with other treatments like Iomab-B might improve outcomes. Additionally, newer treatment strategies targeting specific genetic features of AML have led to better survival rates, indicating potential benefits of personalized approaches. ^{1 2 3 4 5}

How is the Iomab-B + HCT treatment different from other treatments for acute myeloid leukemia?

Iomab-B + HCT is unique because it combines a targeted radiation therapy (Iomab-B) with hematopoietic cell transplantation (HCT), which may offer a more effective approach for patients who are not responding to standard chemotherapy. This treatment aims to deliver radiation directly to the cancer cells, potentially reducing side effects and improving outcomes compared to conventional chemotherapy alone. ^{1 2 3 6 7}

Research Team

Avinash Desai, MD

Principal Investigator

Actinium Pharmaceuticals

Eligibility Criteria

This trial is for people aged 55 or older with active, relapsed, or refractory Acute Myeloid Leukemia (AML) who haven't had a bone marrow transplant before and don't have HIV/HBV/HCV. They need to be in good enough health to participate, have a compatible stem cell donor, and agree to use contraception if of childbearing potential.

Inclusion Criteria

My liver is working well.

Have a central venous catheter line in place

Have an expected survival of > 60 days

Exclusion Criteria

Currently receiving any other active investigational agents

I do not have any serious heart conditions or irregular heartbeats.

I have a serious infection that isn't getting better with antibiotics or antifungals.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Iomab-B with a Reduced Intensity Conditioning regimen and undergo allogeneic hematopoietic stem cell transplant

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Conventional Care
• HCT
• Iomab-B

Trial Overview The study tests Iomab-B followed by a Reduced Intensity Conditioning regimen and hematopoietic stem cell transplant (HCT), compared with conventional care treatments for AML. The goal is to see if Iomab-B can improve outcomes for these patients.

Participant Groups

Group I: Iomab-B Experimental Treatment 2 Interventions

Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT

Group II: Conventional Care Active Control 2 Interventions

Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.

Who Is Running the Clinical Trial?

Actinium Pharmaceuticals

Lead Sponsor

Trials

8

Recruited

290+

Findings from Research

In younger patients with acute myeloid leukemia (AML), combination chemotherapy using anthracycline and cytarabine has shown very good disease control, especially with recent trials suggesting that increasing the dose of anthracycline during induction therapy can enhance outcomes.

While intensive postremission therapy has been effective in improving survival rates, the addition of the targeted therapy gemtuzumab ozogamicin has not led to better results, indicating a need for further research into newer agents that target specific molecular abnormalities in leukemic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New trends in the standard of care for initial therapy of acute myeloid leukemia. Fernandez, HF.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Induction therapy in acute myeloid leukemia: Is it time to put aside standard 3 + 7? [2020]

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

Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high-dose cytarabine-based induction chemotherapy. [2021]

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

New trends in the standard of care for initial therapy of acute myeloid leukemia. [2016]

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

New induction and postinduction strategies in acute myeloid leukemia. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Frontline treatment of acute myeloid leukemia in adults. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Acute leukemia in adults: novel allogeneic transplant strategies. [2012]

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

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG. [2023]