Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

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. 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.

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)

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 Neoplasms, Plasma Cell Cyclophosphamide Fludarabine Lenalidomide bb2121 carfilzomib Dose Escalation

Eligibility

You can join if…

Open to people ages 18 years and up

Subjects must satisfy all of the following criteria to be enrolled in the study:

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

You CAN'T join if...

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:

  1. Subject has non-secretory MM

During Screening:

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

Locations

  • University of California San Francisco (UCSF) accepting new patients
    San Francisco California 94143 United States
  • Mayo Clinic Phoenix accepting new patients
    Scottsdale Arizona 85259 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Celgene
ID
NCT04196491
Phase
Phase 1
Study Type
Interventional
Last Updated