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

Trial Summary

What is the purpose of this trial?

This trial is testing a cancer treatment called S-TT3, which uses high-dose chemotherapy to kill cancer cells. It targets patients needing strong chemotherapy and transplants. The goal is to reduce severe side effects while maintaining treatment effectiveness.

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.

What data supports the effectiveness of the TT3-LITE Regimen (L-TT3) treatment for multiple myeloma?

Research shows that similar regimens like VTd-PACE and VTD-PACE are effective in treating difficult cases of multiple myeloma, with high response rates and improved survival times. These treatments have been used successfully as a bridge to further therapies, indicating potential effectiveness for the TT3-LITE Regimen. ^{1 2 3 4 5}

What safety data exists for the TT3-LITE Regimen or its components?

The safety data for components like volasertib, used in similar regimens, shows increased risks of infections and fever, with some serious side effects like myelosuppression (a decrease in bone marrow activity) leading to higher early mortality. However, midostaurin, another component, has shown a manageable safety profile with common side effects like nausea and diarrhea. ^{6 7 8 9 10}

How is the TT3-LITE treatment for multiple myeloma different from other treatments?

The TT3-LITE treatment, involving the M-VTD-PACE regimen, is unique because it combines multiple drugs to target difficult-to-treat relapsed or refractory multiple myeloma, especially when other modern therapies have been exhausted. This regimen is used as a 'salvage therapy' to bridge patients to subsequent treatments, showing effectiveness in improving renal function and achieving a high overall response rate in heavily pre-treated patients. ^{1 2 3 11 12}

Research Team

Maurizio Zangari, MD

Principal Investigator

UAMS

Maurizio Zangari, MD

Principal Investigator

UAMS

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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]

References

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

First line and salvage therapy with total therapy 3-based treatment for multiple myeloma- an extended single center experience. [2014]

2. Greece pubmed.ncbi.nlm.nih.gov

High efficacy and safety of VTD as an induction protocol in patients with newly diagnosed multiple myeloma eligible for high dose therapy and autologous stem cell transplantation: A report of the Polish Myeloma Study Group. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience. [2023]

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

Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphamide-etoposide as a Salvage and Bridging Regimen before Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Multiple Myeloma. [2022]

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

Coping with toxicities of docetaxel (Taxotere). [2020]

7. United States 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. [2022]

8. United States 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. [2021]

9. United States 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. [2015]

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

Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial. [2021]

11. United States 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. [2022]

12. United States 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. [2023]