Clinical Trials /

Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma

NCT04756726

Description:

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 administered orally in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM) administered once a day (QD) as a single agent and in combination with dexamethasone.

Related Conditions:
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma
  • Official Title: A Phase 1/2 Open-Label Multi-Center Study to Characterize the Safety and Tolerability of CFT7455 in Subjects With Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CFT7455-1101
  • NCT ID: NCT04756726

Conditions

  • Multiple Myeloma
  • Lymphoma, Non-Hodgkin's

Interventions

DrugSynonymsArms
CFT7455Phase 1: Arm A - CFT7455
Dexamethasone OralPhase 1: Arm B2 - CFT7455 in combination with dexamethasone

Purpose

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 administered orally in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM) administered once a day (QD) as a single agent and in combination with dexamethasone.

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Arm A - CFT7455ExperimentalParticipants with r/r NHL or r/r MM will be treated with oral CFT7455 QD
  • CFT7455
Phase 1: Arm B1 - CFT7455ExperimentalParticipants with r/r MM will be treated with oral CFT7455 QD until the determination of maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
  • CFT7455
Phase 1: Arm B2 - CFT7455 in combination with dexamethasoneExperimentalParticipants with r/r MM will be treated with oral CFT7455 in combination with a fixed dose of oral dexamethasone in each cohort
  • CFT7455
  • Dexamethasone Oral
Phase 1: Arm C - CFT7455ExperimentalParticipants with r/r NHL will be treated with oral CFT7455 QD in each cohort until determination of MTD/RP2D
  • CFT7455
Phase 2: Arm 1 - CFT7455ExperimentalParticipants with r/r MM will be treated with oral CFT7455
  • CFT7455
Phase 2: Arm 2 - CFT7455 in combination with dexamethasoneExperimentalParticipants with r/r MM treated with oral CFT7455 in combination with oral dexamethasone
  • CFT7455
  • Dexamethasone Oral
Phase 2: Arm 3 - CFT7455ExperimentalParticipants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455
  • CFT7455
Phase 2: Arm 4 - CFT7455ExperimentalParticipants with r/r peripheral T-cell lymphoma (PTCL) treated with oral CFT7455
  • CFT7455

Eligibility Criteria

        Inclusion Criteria:

          1. Be willing and able to provide signed informed consent for the trial.

          2. Age ≥18 years at the time of signed consent.

          3. Have histologically or cytologically-confirmed NHL or MM that is r/r disease and must
             not be candidates for regimens known to provide clinical benefit to be eligible for
             the study.

          4. MM subject must have a documented diagnosis of MM and measurable disease at
             enrollment. Measurable disease is defined as:

               -  M-protein ≥0.5g/dL by Serum Protein Electrophoresis (sPEP) or

               -  ≥200mg/24-hour urine collection by Urine Protein Electrophoresis (uPEP) or

               -  Serum Free Light Chain (FLC) levels >100 mg/L involved light chain and an
                  abnormal kappa/lambda (κ/λ) ratio in subjects without measurable serum or urine
                  M-protein or

               -  For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be
                  reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥
                  0.50g/dL.

          5. Prior treatments for MM subjects must have the following:

               -  Received at least 3 prior anti-myeloma regimens including at least 2 consecutive
                  cycles of lenalidomide, pomalidomide, a proteasome inhibitor a glucocorticoid and
                  an anti-CD38 antibody (induction with or without a bone marrow transplant with or
                  without maintenance therapy is considered one regimen).

               -  Refractory disease defined as disease that is nonresponsive to therapy (failure
                  to achieve minimal response or development of progressive disease) or disease
                  progression within 60 days from the last dose of their last myeloma therapy.

          6. NHL subjects must have documented diagnosis of NHL and measurable disease defined by
             measurable disease (consistent with Lugano classification) defined as at least one
             lesion that can be accurately measured in at least two dimensions with PET-CT,
             documented within 4 weeks of their projected cycle one day one (C1D1) visit. Minimum
             measurement must be >15 mm in the longest diameter.

          7. NHL subjects must have received the following regarding prior therapy:

               -  Peripheral T-cell Lymphoma: At least one prior line containing alkylator-based
                  chemotherapy. Note: For subjects with Anaplastic Large Cell Lymphoma (ALCL), the
                  subject must also have received CD30 antibody therapy.

               -  Mantle Cell Lymphoma: ≥2 lines of therapy, including CD20 antibody and alkylator
                  chemotherapy, and a Bruton's tyrosine kinase (BTK) inhibitor.

               -  Follicular Lymphoma: ≥2 lines of therapy, including CD20 antibody therapy and
                  alkylator chemotherapy.

               -  Diffuse Large B-cell Lymphoma: ≥2 lines of therapy, including prior CD20 antibody
                  therapy, and has received prior autologous bone marrow transplant (or is
                  ineligible for bone marrow transplant).

               -  Other NHL: Subjects must have been treated with all standard of care therapies
                  available to the subject which, in the assessment of the investigator, may be
                  beneficial to the subject.

          8. A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               -  A woman of non-childbearing potential (i.e., physiologically incapable of
                  becoming pregnant) defined as pre-menopausal females with a documented tubal
                  ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous
                  amenorrhea [in questionable cases a blood sample with simultaneous follicle
                  stimulating hormone (FSH) > 40 MIU/mL and estradiol < 40 pg/mL (<147 pmol/L) must
                  be obtained].

               -  Females on hormone replacement therapy (HRT) and whose menopausal status is in
                  doubt will be required to use one of the contraception methods specified in the
                  study protocol if they wish to continue their HRT during the study. Otherwise,
                  they must discontinue HRT to allow confirmation of postmenopausal status prior to
                  study enrollment.

               -  Agree to having ongoing pregnancy tests during the study and after
                  discontinuation of the study.

          9. A male participant must have either had a prior vasectomy or agree to use a condom
             during the treatment period and for at least 90 days after the last dose of study
             treatment.

        Exclusion Criteria:

          1. Presence of central nervous system (CNS) disease.

          2. Has received prior radiotherapy within 2 weeks of start of study treatment.

          3. Have active pneumonitis.

          4. Have any of the following:

               -  Non-secretory or oligosecretory MM

               -  Plasma cell leukemia

               -  Systemic light chain amyloidosis

               -  Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin
                  changes (POEMS) Syndrome

               -  Lymphoblastic lymphoma

               -  Mycosis fungoides

               -  Sezary syndrome

               -  Primary cutaneous T-cell lymphomas

               -  Primary CNS lymphoma

               -  B-cell or T-cell prolymphocytic leukemia

          5. Subjects with a peripheral neuropathy ≥ Grade 2.

          6. Known malignancy other than study indication that is progressing or has required
             treatment within the past three years.

          7. Received live, attenuated vaccine within four weeks of first dose.

          8. Known history of human immunodeficiency virus (HIV) infection. No HIV testing is
             required unless mandated by local health authority.

          9. Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc)
             antigen.

         10. Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of
             viral load. If hepatitis C antibody test is positive, a confirmatory test should be
             performed. If the test is negative, subject is eligible for this trial.

         11. Concurrent administration of strong CYP3A modulators.

         12. Is pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment.

         13. Subjects on proton pump inhibitors (PPIs). The last dose of PPIs must be administered
             seven days prior to administration of study drug. Antacids are acceptable when
             administered in a staggered dosing manner with CFT7455.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Safety and tolerability of CFT7455
Time Frame:Days 1-28
Safety Issue:
Description:Percent of subjects with adverse events (AEs) with CFT7455 as a single agent

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:C4 Therapeutics, Inc.

Trial Keywords

  • Multiple Myeloma
  • Lymphoma, Non-Hodgkin's
  • CFT7455
  • Relapsed
  • Refractory

Last Updated

February 16, 2021