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Multiple MyelomaPhase 2NCT02128230

UARK 2012-02 Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission

A Phase 2 study testing myPRS, Induction 1 - MEL-10+CFZ-TD-PACE and First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic) in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to improve the clinical outcomes of research subjects with high-risk multiple myeloma in the context of the immediately preceding Total therapy 5 trial 2008-02 and Total therapy 3 trials 2003-33 and 2006-66. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Multiple Myeloma
What is being tested?
myPRS, Induction 1 - MEL-10+CFZ-TD-PACE and First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
10 Jun 2014to 19 Feb 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have newly diagnosed active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy.
  • Patients must be either untreated or have not had more than one cycle of systemic MM therapy, excluding bisphosphonates and localized radiation.
  • Participants must have high-risk disease, as defined by GEP70 risk score of ≥ 0.66
  • Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.
  • Patients must have a platelet count of ≥ 50,000/μL, unless lower levels are explained by extensive bone marrow plasmacytosis.
  • Patients must be at least 18 years of age and not older than 75 years of age at the time of registration.
Show all 10Show fewer
  • Participants must have preserved renal function as defined by a serum creatinine level of < 3 mg/dL.
  • Participants must have an ejection fraction by ECHO or MUGA scan ≥ 45%
  • Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted if the principal investigator documents that the patient is a candidate for high dose therapy.
  • Patients must have signed an IRB-approved informed consent indicating their understanding of the proposed treatment and understanding that the protocol has been approved by the IRB.

Who cannot join

  • Does not have high-risk disease
  • Poorly controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
  • Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years.
  • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Subjects of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

Other trials in United States

About this study

Official title: A Phase II Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) by Applying Non-Host-Exhausting and Timely Dose-Reduced Mel-80-CFZ-TD-Pace Transplant(s) With Interspersed Mel-20-CFZ-TD-Pace With CFZ-RD and CFZ-D Maintenance

The purpose of this study is to improve the clinical outcomes of research subjects with high-risk multiple myeloma in the context of the immediately preceding Total therapy 5 trial 2008-02 and Total therapy 3 trials 2003-33 and 2006-66.

Read the detailed description

Total therapy 5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission by reducing host-imposed toxicity and facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib. This will result in avoiding multiple myeloma re-growth that, we postulate, ensued in Total therapy 3 during recovery phases from severe de-conditioning. It is speculated that the incidence of positive minimal residual disease will be reduced with the addition of one cycle of consolidation therapy. The following approach will be implemented:

  • apply a 4-day fractionated lower dose melphalan (80 mg/m2) together with CFZ-TD-PACE regimen in MEL80-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE as a hopefully less toxic and more effective transplant regimen
  • interspersed with 1 cycle of non-transplant supported MEL-20-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE (in lower doses than with transplant) inter-therapy (reduced from two cycles due to prolonged thrombocytopenia)
  • followed by CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE consolidation therapy post transplant #2
  • CFZ-RD (carfilzomib, lenalidomide and dexamethasone) maintenance for 1 year followed by CFZ-D for an additional year
Being tested
myPRS, Induction 1 - MEL-10+CFZ-TD-PACE, First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic), Inter-Therapy - MEL-20+CFZ-TD-PACE (75%), Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)
Keywords
High-Risk, Carfilzomib
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • myPRSDevice

    Also called Gep70

    Genome expression profiling used to identify high-risk and low-risk multiple myeloma

  • Induction 1 - MEL-10+CFZ-TD-PACEDrug

    Also called Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®)

    Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.

    Regimen: CFZ 20 mg/m2 on days 1, 5, \& 6; MEL 10mg/m2 on day 3; T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 400 mg/m2/d, and E 40 mg/m2/d on days 5-8; G-CSF 10 mcg/kg/day from day 11 through end of Peripheral Blood Stem Cell (PBSC) collection.

    Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 1st transplant.

  • First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)Drug

    Also called Autologous Peripheral Blood Stem Cell Transplant, Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®)

    Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.

    Regimen: CFZ 20 mg/m2 on days -5 \& -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 \& -2; PBSC transplant on day 0.

    Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until inter-therapy.

  • Inter-Therapy - MEL-20+CFZ-TD-PACE (75%)Drug

    Also called Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®)

    Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.

    Regimen: CFZ 27 mg/m2 on days 1-2; MEL 5 mg/m2/d, T 200 mg/d, D 20 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 75 mg/m2/d, and E 60 mg/m2/d on days 1-4.

    Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 2nd transplant.

  • Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)Drug

    Also called Autologous Peripheral Blood Stem Cell Transplant, Melphalan (Alkeran™), Carfilzomib (Kyprolis®), Thalidomide (Thalomid®)

    Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.

    Regimen: CFZ 20 mg/m2 on days -5 \& -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 \& -2; PBSC transplant on day 0.

    Optional Bridging with T 50mg/d and D 20 mg on day 1-4 every 21 days until consolidation.

  • Consolidation - CFZ-TD-PACEDrug

    Also called Carfilzomib (Kyprolis®), Thalidomide (Thalomid®), Dexamethasone (Decadron®), Cisplatin (CDDP) (Platinol®)

    Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), adriamycin (A), cyclophosphamide (C) and etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter.

    Regimen: CFZ 27 mg/m2 on days 1-2; T 200 mg/d, D 40 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 300 mg/m2/d, and E 30 mg/m2/d on days 1-4.

  • Maintenance - CFZ-R(T)-DDrug

    Also called Carfilzomib (Kyprolis®), Lenalidomide (CC-5013) (Revlimid®), Dexamethasone (Decadron®), Thalidomide (Thalomid®)

    Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) and lenalidomide (R) are capsules and dexamethasone (D) is a pill; all will be taken by mouth.

    Regimen: For Cycles 1-12 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, \& 22; lenalidomide (R) 15 mg/d on days 1-21. For Cycles 13-24 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, \& 22. T may be substituted for R at 100 mg/day at the treating physician's discretion.

Study groups in NCT02128230
Study groupRoleWhat they receive
Total Therapy 5bExperimentalInduction, optional bridging, first transplant, optional bridging, inter-therapy, optional bridging, second transplant, optional bridging, consolidation, maintenance
Receives: Device: myPRS; Drug: Induction 1 - MEL-10+CFZ-TD-PACE; Drug: First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Drug: Inter-Therapy - MEL-20+CFZ-TD-PACE (75%); Drug: Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Drug: Consolidation - CFZ-TD-PACE; Drug: Maintenance - CFZ-R(T)-D

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Remission Rate for Participants With High-risk Myeloma

    Toward improving the clinical outcomes of research subjects with high-risk MM (HR-MM) in the context of the immediately preceding TT5 trial 2008-02 and TT3 trials 2003-33 and 2006-66, TT5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission (AS-CR-2) by reducing host-imposed toxicity and thus facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib (CFZ). This will result in avoiding MM re-growth that, we postulate, ensued in TT3 during recovery phases from severe de-conditioning. Furthermore, we speculate that the incidence of positive minimal residual disease (MRD) will be reduced with the addition of one cycle of consolidation therapy.

    Measured: from baseline to either death or study completion for each subject (up to approximately 48 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2014 (estimated)
  2. Study start10 Jun 2014
  3. Primary completion19 Feb 2019
  4. Study completion19 Feb 2019

Why it stopped: Low enrollment and Futility as determined by Amgen's Carfilzomib NASCR program.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02128230
Sponsor's protocol ID
134668
Status last verified
Apr 2021
First submitted
29 Apr 2014
Last updated
22 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

    PubMed 33357481

  • Davies FE, Rosenthal A, Rasche L, Petty NM, McDonald JE, Ntambi JA, Steward DM, Panozzo SB, van Rhee F, Zangari M, Schinke CD, Thanendrarajan S, Walker B, Weinhold N, Barlogie B, Hoering A, Morgan GJ. Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Haematologica. 2018 Jun;103(6):1047-1053. doi: 10.3324/haematol.2017.177139. Epub 2018 Mar 22.

    PubMed 29567784

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing myPRS, Induction 1 - MEL-10+CFZ-TD-PACE and First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic) in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Remission Rate for Participants With High-risk Myeloma (time frame: from baseline to either death or study completion for each subject (up to approximately 48 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02128230, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.

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