Iomab-B + HCT for Acute Myeloid Leukemia

(SIERRA Trial)

Not currently recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, Iomab-B, for individuals with hard-to-treat Acute Myeloid Leukemia (AML). It compares Iomab-B, combined with a special type of stem cell transplant called Hematopoietic Cell Transplantation (HCT), to standard chemotherapy options. The researchers aim to determine if Iomab-B can improve outcomes for those whose AML has relapsed or is resistant to other treatments. Ideal participants include those with active, relapsed, or refractory AML who have not succeeded with standard therapies. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

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.

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

Research has shown that Iomab-B was well-tolerated in past studies. In one study, 75% of patients experienced few side effects, with not many unwanted reactions reported. This suggests that Iomab-B is generally safe for patients. Additionally, Iomab-B has been tested in over 400 patients, demonstrating longer survival and good tolerance. The safety data appears promising for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Iomab-B is unique because it uses a radioactive isotope to specifically target and eliminate cancerous cells in patients with Acute Myeloid Leukemia (AML). This approach is different from conventional chemotherapy, which affects both cancerous and healthy cells, often leading to more severe side effects. Iomab-B is administered alongside a Reduced Intensity Conditioning regimen before a stem cell transplant, potentially making the transplant process more effective and reducing the risk of the cancer returning. Researchers are excited about Iomab-B because this targeted therapy could improve outcomes and increase the number of patients eligible for a potentially curative transplant.

What evidence suggests that this trial's treatments could be effective for Acute Myeloid Leukemia?

Research has shown that Iomab-B, one of the treatments studied in this trial, when combined with a less intense preparation and a stem cell transplant, yields promising results for treating Acute Myeloid Leukemia (AML). In one study, 22% of patients achieved a lasting complete remission (dCR) at six months with Iomab-B, compared to 0% in the conventional care arm of this trial. Additionally, patients receiving Iomab-B had an average survival time of 6.4 months, while those on conventional care averaged only 3.2 months. These findings suggest that Iomab-B might offer better chances of survival and remission for AML patients, particularly those with recurrent or treatment-resistant disease. ^{1 3 5 6 7}

Who Is on the Research Team?

Avinash Desai, MD

Principal Investigator

Actinium Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241491

Survival Outcomes and Dosimetric Analysis of Iomab-B (131I ... The median overall survival (OS) for pts in the Iomab-B group, who were TP53 negative was 6.37 mos compared to 5.72 mos for those with TP53 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0928125824003103

Outcomes and radiation safety of Iomab-B (131I ... The primary endpoint of durable CR (dCR) at 6 months strongly favored Iomab-B with 22% dCR vs. 0% for CC (p < 0.0001). Iomab-B followed by HCT was well ...

3. ir.actiniumpharma.com ir.actiniumpharma.com/press-releases/detail/467/actinium-announces-iomab-b-produces-high-response-rates-and

Actinium Announces Iomab-B Produces High Response ... The results also show that on a population basis and across subgroups, an Iomab-B led BMT may result in improved survival. We are incredibly ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02665065

NCT02665065 | Study of Iomab-B vs. Conventional Care in ... The SIERRA trial has a primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival following randomization ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428510/

S248: SIERRA TRIAL RESULTS WITH A TARGETED ... The median overall survival (OS) was 6.4 vs 3.2 mos for pts receiving Iomab-B-based conditioning followed by HSCT vs non-CO pts on CC arm, respectively. Median ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/P685

Safety and efficacy results from the pivotal phase 3 SIERRA trial The primary endpoint of dCR at 6 months strongly favored Iomab-B with 22% dCR vs. 0% for CC (p<0.0001) and event-free survival (EFS) at 6 months was 26% vs. 0.2 ...

7. prnewswire.com prnewswire.com/news-releases/safety-data-highlighting-low-rates-of-adverse-events-and-non-relapse-transplant-related-mortality-in-patients-receiving-iomab-b-presented-at-2021-snmmi-virtual-conference-301312395.html

Safety Data Highlighting Low Rates of Adverse Events and ... Importantly, Iomab-B has been well tolerated and we are elated with the safety data from 75% of patient enrollment in the SIERRA trial. Given ...