TT3-LITE Regimen for Multiple Myeloma

(TT4B Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Arkansas

Must not be taking: Bortezomib, Boron, Mannitol

Disqualifiers: Hypertension, Diabetes, Heart disease, 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

382 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the standard treatment for multiple myeloma (a type of blood cancer) can be made safer by reducing side effects while maintaining effectiveness. The trial currently tests the standard treatment regimen, known as the TT3-LITE Regimen (L-TT3), which includes several cycles of therapy, a type of blood cell collection, and long-term maintenance treatment. Suitable candidates for this trial are those newly diagnosed with active multiple myeloma who have not received more than one cycle of treatment. As a Phase 3 trial, this research represents the final step before FDA approval, offering patients a chance to contribute to the development of a potentially safer treatment option.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer.

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

Research has shown that the TT3-LITE treatment plan yields promising results for patients with multiple myeloma, a type of blood cancer. In earlier studies, 88% of patients responded well to the treatment, indicating it is generally well-tolerated and aims to reduce treatment-related side effects by half.

M-VTD-PACE, a component of the TT3-LITE plan, has also undergone research. After two years, 83% of patients achieved a nearly complete response, with many experiencing longer survival. However, some patients faced issues such as hospital readmissions, which can occur with intensive treatments.

Overall, these findings suggest that while both treatments have been effective, safety and side effects remain important considerations for potential trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard multiple myeloma treatments that typically involve several cycles of induction therapy, the TT3-LITE Regimen (L-TT3) is unique because it employs only one cycle of induction therapy with M-VTD-PACE. This streamlined approach not only potentially reduces the treatment burden for patients but also aims to maintain effectiveness with less intensive therapy. Researchers are excited about this treatment as it could offer a more efficient and patient-friendly option without compromising the therapeutic benefits.

What is the effectiveness track record for the standard TT3 regimen in treating multiple myeloma?

Research has shown that the TT3-LITE treatment plan for multiple myeloma, which participants in this trial may receive, yields promising results. Earlier studies of the TT3 program, which uses bortezomib and thalidomide, reported a high rate of long-lasting complete response (CR) in patients. Specifically, 90% of patients maintained this complete response for four years, indicating a strong and lasting effect of the treatment, which suggests its effectiveness.

Additionally, the M-VTD-PACE treatment, part of the TT3 program and included in the standard TT3 regimen arm of this trial, has also proven effective. Studies found that 83% of patients achieved a near-complete response within two years, with 84% not experiencing major issues and 86% still alive. These results support the potential effectiveness of this treatment in managing multiple myeloma. ^{1 5 6 7 8}

Who Is on the Research Team?

Maurizio Zangari, MD

Principal Investigator

UAMS

Maurizio Zangari, MD

Principal Investigator

UAMS

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with newly diagnosed, active Multiple Myeloma that requires treatment and have low-risk disease characteristics. They should not have had more than one cycle of systemic therapy and must be in good general health with proper organ function.

Inclusion Criteria

I have newly diagnosed active multiple myeloma needing treatment, or my smoldering myeloma has progressed and now requires chemotherapy.

My kidney, heart, and lung functions meet the required levels.

My cancer is considered low-risk based on specific genetic and health markers.

Exclusion Criteria

My cancer is considered high risk based on specific genetic test results.

I have no cancer history, except for certain skin cancers or in situ cervical cancer, and have been cancer-free for 3 years if I had another type.

I do not have severe low platelets, nerve damage, allergies to certain drugs, recent heart issues, chronic lung disease, light chain disease, or high creatinine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with M-VTD-PACE, followed by PBSC collection after the 1st cycle

6-12 weeks

Tandem Transplant

MEL-based tandem transplant administered 6 weeks to 3 months apart with single dose MEL 200 mg/m2

6 weeks to 3 months

Consolidation Therapy

Participants receive 2 cycles of dose-reduced VTD-PACE

8-12 weeks

Maintenance Therapy

Maintenance treatment with VRD for 3 years

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• M-VTD-PACE
• TT3-LITE Regimen (L-TT3)

Trial Overview The study initially aimed to compare a standard treatment (S-TT3) with a less intense version (L-TT3) to see if side effects could be halved. However, it's now only enrolling patients for the S-TT3 after discontinuing randomization into L-TT3.

How Is the Trial Designed?

Group I: ARM B Experimental Treatment 1 Intervention

The TT3-LITE Regimen (L-TT3) will employ only 1 cycle of induction therapy with MVTD- PACE

Group II: ARM A Active Control 1 Intervention

The standard TT3 Regimen (S-TT3) will consist of 2 cycles of induction therapy with M-VTD-PACE and PBSC collection after the 1st cycle. MEL-based tandem transplant will be administered 6 weeks to 3 months apart, applying single dose MEL 200 mg/m2 with adjustments for age and renal function. Consolidation will consist of 2 cycles of dose-reduced VTD-PACE. Maintenance treatment will employ VRD for 3 years.

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Published Research Related to This Trial

In patients with newly diagnosed multiple myeloma, the modified regimen of bortezomib, thalidomide, and dexamethasone (VTd-mod) using a lower thalidomide dose (100 mg/day) was found to be noninferior to the traditional higher dose (VTd-label) in terms of overall survival and progression-free survival, while showing better post-transplant response rates.

The combination of daratumumab with the VTd regimen (D-VTd) demonstrated superior efficacy compared to the traditional VTd-label, while maintaining similar safety profiles, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. Moreau, P., Hulin, C., Zweegman, S., et al.[2023]

Midostaurin, a multikinase inhibitor, was found to have a manageable safety profile in a study of 103 patients with FLT3 mutation-positive acute myeloid leukemia, with no new safety events reported during treatment.

The treatment showed promising outcomes, including high rates of transplant success and low relapse rates during maintenance therapy, indicating its efficacy when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program. Roboz, GJ., Strickland, SA., Litzow, MR., et al.[2021]

In a phase 2 trial involving 87 older patients with acute myeloid leukemia (AML), the combination of low-dose cytarabine (LDAC) and volasertib showed a higher response rate (31.0%) compared to LDAC alone (13.3%), indicating improved efficacy of the combination treatment.

The combination therapy also significantly prolonged median event-free survival (5.6 months vs. 2.3 months) and overall survival (8.0 months vs. 5.2 months) compared to LDAC alone, although it was associated with a higher frequency of adverse events, particularly neutropenic fever and gastrointestinal issues, without increasing the death rate at 60 and 90 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy. Döhner, H., Lübbert, M., Fiedler, W., et al.[2022]

In a phase II study involving 98 patients with untreated multiple myeloma, both the bortezomib-thalidomide-dexamethasone (VTD) and the cyclophosphamide-added regimen (VTDC) showed high rates of near-complete response (nCR) or better, with 51% and 44% respectively, indicating both regimens are effective induction therapies.

However, the addition of cyclophosphamide in VTDC led to increased toxicity, with higher rates of grade 3 to 4 adverse events (57% vs 47% for VTD) and no significant improvement in treatment efficacy, suggesting that VTD may be the safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. Ludwig, H., Viterbo, L., Greil, R., et al.[2022]

In a study of 31 pediatric patients with relapsed acute lymphoblastic leukemia (ALL), topotecan administered before standard induction therapy resulted in an impressive 89.3% response rate, significantly reducing circulating blast cells.

The combination of topotecan with standard induction therapy led to a 74.2% complete response rate, indicating that this regimen is effective and well-tolerated, despite some hematologic and gastrointestinal toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse. Hijiya, N., Stewart, CF., Zhou, Y., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9667441/

VTd-PACE and VTd-PACE-like regimens are effective salvage ... After 2 years, 83% of patients achieved a near-complete response and a 2-year estimated event-free survival and OS of 84% and 86%, respectively, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123132216

Real-World Clinical Outcomes in Patients with Relapse ... This retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE at the ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37668787/

Real-world clinical outcomes in patients with relapsed and ... Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT116010

Clinical outcomes after intensive VDT-PACE therapy for ... The median overall survival (OS) post-VDTPACE was 8.2 months (95% CI, 5.7-10.9). ... Thirty eight of 66 (57.6%) patients were rehospitalized after initial ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.24954

Efficacy of VDT PACE‐like regimens in treatment ... Patients received a median of 1 cycle (range 1-9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9175829/

Outcomes of VDPACE with an immunomodulatory agent as a ... After a median follow‐up of 51.4 months, the median overall survival (OS) and progression‐free survival were 14.9 months (95% CI: 7.8‐NA) and 5.5 months (95% CI ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001065

Outcomes of Patients With Extramedullary Disease in ... We report effectiveness outcomes and safety in patients with and without EMD from the pooled analysis of LocoMMotion and MoMMent.

8. researchgate.net researchgate.net/publication/373687562_Real-world_clinical_outcomes_in_patients_with_relapsed_and_refractory_multiple_myeloma_receiving_VTD-PACE_treatment_in_the_era_of_monoclonal_antibodies

Real-world clinical outcomes in patients with relapsed and ... Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and ...