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Multiple MyelomaPhase 1KarMMa-4NCT04196491

A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM)

A Phase 1 study testing bb2121, Fludarabine and Cyclophosphamide in people with Multiple Myeloma, run by Celgene at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG criteria) NDMM. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
bb2121, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
22 sitesUnited States
Study dates
27 May 2020to 7 Jun 2023
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must satisfy all of the following criteria to be enrolled in the study:
  • Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
  • Subject is ≥ 18 years of age at the time of initial diagnosis of MM
  • Subject has measurable disease at initial diagnosis by
  • M-protein and/or
  • Light chain MM without measurable disease in the serum or urine
Show all 13Show fewer
  • Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:
  • ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
  • ISS Stage III and serum LDH > ULN
  • Subject has Eastern Cooperative Oncology Group performance ≤ 1
  • Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment:
  • Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
  • Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)

Who cannot join

  • The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment:
  • At initial diagnosis, screening and prior to initiation of induction therapy for MM:
  • Subject has non-secretory MM
  • During Screening:
  • Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
  • Subject has any of the following laboratory abnormalities:
Show all 30Show fewer
  • Absolute neutrophil count < 1,000/μL
  • Platelet count < 50,000 mm3
  • Hemoglobin < 8 g/dL (< 4.9 mmol/L)
  • Serum creatinine clearance < 45 mL/min
  • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
  • Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal
  • Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
  • INR or aPTT > 1.5 × ULN
  • Subject has history or presence of clinically significant CNS pathology
  • Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
  • Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
  • Subjects has moderate or severe pulmonary hypertension
  • Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
  • Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening
  • Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment
  • Subject has cardiac conditions such as:
  • Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45%
  • Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities
  • Subject has Pulmonary conditions such as:
  • Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.
  • Inadequate pulmonary function defined as oxygen saturation < 92 % on room air
  • Subject needs ongoing treatment with chronic immunosuppressants
  • Subject has history of primary immunodeficiency
  • Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • Local Institution - 108

    Atlanta, Georgia, 30322

  • Local Institution - 123

    Atlanta, Georgia, 30342

  • Local Institution - 115

    Boston, Massachusetts, 02114

  • Local Institution - 122

    Boston, Massachusetts, 02215

  • Local Institution - 120

    Charlotte, North Carolina, 28207

  • Local Institution - 102

    Dallas, Texas, 75390

  • Local Institution - 106

    Denver, Colorado, 80218

  • Local Institution - 117

    Hackensack, New Jersey, 07601

  • Local Institution - 114

    Houston, Texas, 77030

  • Local Institution - 101

    Jacksonville, Florida, 32224

  • Local Institution - 110

    Los Angeles, California, 90095

  • Local Institution - 107

    Milwaukee, Wisconsin, 53226-3522

  • Local Institution - 103

    Nashville, Tennessee, 37203

  • Local Institution - 121

    New York, New York, 10016

  • Local Institution - 109

    New York, New York, 10029

  • Local Institution - 124

    New York, New York, 10065

  • Local Institution - 118

    Philadelphia, Pennsylvania, 19104

  • Local Institution - 119

    Phoenix, Arizona, 85054

  • Local Institution - 112

    Portland, Oregon, 97239

  • Local Institution - 116

    San Francisco, California, 94143

  • Local Institution - 104

    Seattle, Washington, 98109-1024

  • Local Institution - 113

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Multicenter Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (KarMMa-4)

This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG criteria) NDMM. Subjects should have received 3 Cycles of standard induction therapy prior to undergoing leukapheresis procedure to collect autologous mononuclear cells for manufacture of the drug product (bb2121). Following manufacture of the drug product, subjects will receive fourth cycle of induction therapy followed by lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. Maintenance therapy is recommended for all subjects who have received bb2121 infusion and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later.

Keywords
Multiple Myeloma, Newly diagnosed multiple myeloma, BB2121, KarMMa-4, Phase I, NDMM, High Risk, R-ISS III, KRd, RVd, Dara-KRd, Dara-RVd, CyBorD, BCMA
Medical subject headings
Multiple Myeloma

What participants receive

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

Study groups in NCT04196491
Study groupRoleWhat they receive
Dose EscalationExperimental* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Receives: Biological: bb2121; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Lenalidomide

What is being measured

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

  1. Dose-limiting toxicity (DLT) rates

    DLTs will be assessed during the DLT interval (ie, within 21 days immediately after bb2121 infusion). DLTs are defined as any bb2121 related Grade 3 to 5 toxicity.

    Measured: Up to completion of DLT period after last subject bb2121 infused

  2. Adverse Events (AEs)

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

    Measured: Approximately 2 years after last subject bb2121 infused

Secondary outcomes (11)

  1. Proportion of subjects who achieved Complete Response (CR) Rate

    Is defined as proportion of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma for multiple myeloma will be determined by an Investigator assessment.

    Measured: Approximately 2 years after last subject bb2121 infused

  2. Overall Response Rate (ORR)

    Is defined as proportion of subjects who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as determined by an Investigator assessment

    Measured: Approximately 2 years after last subject bb2121 infused

  3. Duration of Response (DoR)

    Is defined as time from first documentation of response (PR or better) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first, for responders.

    Measured: Approximately 2 years after last subject bb2121 infused

  4. Time to Complete Response (TCR)

    Is defined as time from bb2121 infusion date to first documentation of CR for responders (Complete Response (CR) or better).

    Measured: Approximately 2 years after last subject bb2121 infused

  5. Time to start maintenance

    Is defined as time to start lenalidomide maintenance therapy post-bb2121 infusion

    Measured: Approximately 2 years after last subject bb2121 infused

  6. Feasibility of initiating maintenance

    Number of subjects starting the maintenance or on maintenance between D90 and D110

    Measured: Approximately 2 years after last subject bb2121 infused

  7. Progression-free Survival (PFS)

    Is defined as time from bb2121 infusion date to first documentation of PD, or death due to any cause, whichever occurs first.

    Measured: Approximately 2 years after last subject bb2121 infused

  8. Overall Survival (OS)

    Is defined as time from bb2121 infusion date to time of death due to any cause

    Measured: Approximately 2 years after last subject bb2121 infused

  9. Pharmacokinetics - Cmax

    Maximum transgene level

    Measured: Approximately 2 years after last subject bb2121 infused

  10. Pharmacokinetics - Tmax

    Time to peak transgene level

    Measured: Approximately 2 years after last subject bb2121 infused

  11. Pharmacokinetics - AUC

    Area under the curve of the transgene level

    Measured: Approximately 2 years after last subject bb2121 infused

Timeline

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

  1. First posted12 Dec 2019
  2. Study start27 May 2020
  3. Primary completion7 Jun 2023
  4. Study completion7 Jun 2023

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04196491
Sponsor's protocol ID
BB2121-MM-004
Other IDs
U1111-1243-5088
Acronym
KarMMa-4
Status last verified
Aug 2023
First submitted
10 Dec 2019
Last updated
23 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Publications

  • Parmar H, Vesole DH, Biran N. From VAD to VRD: Is Transplant Still Needed in the Upfront Setting of Myeloma? Cancer J. 2021 May-Jun 01;27(3):190-195. doi: 10.1097/PPO.0000000000000522.

    PubMed 34549906

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bb2121, Fludarabine and Cyclophosphamide in people with Multiple Myeloma, run by Celgene at 22 sites 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 13 inclusion and 30 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: finished, as of the sponsor's last update on 23 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose-limiting toxicity (DLT) rates (time frame: Up to completion of DLT period after last subject bb2121 infused). The study lists 2 primary outcomes in all. 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 NCT04196491, which also lists 1 linked publication.

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 23 Aug 2023.

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