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Testing the Addition of an Anti-cancer Drug, Hu5F9-G4 (Magrolimab), to the Usual Chemotherapy Treatment (Mogamulizumab) in T-Cell (a Type of Immune Cell) Lymphoma That Has Returned After Treatment or Does Not Respond to Treatment

NCT04541017

Description:

This phase Ib/II trial identifies the best dose and possible benefits and/or side effects of magrolimab when given in combination with mogamulizumab in treating patients with stage IB-IV mycosis fungoides or Sezary syndrome types of T-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Magrolimab and mogamulizumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Treatment with magrolimab in combination with mogamulizumab may stabilize cancer for longer period than the usual treatment in patients with relapsed/refractory T-cell lymphoma who have been previously treated.

Related Conditions:
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Testing the Addition of an Anti-cancer Drug, Hu5F9-G4 (Magrolimab), to the Usual Chemotherapy Treatment (Mogamulizumab) in T-Cell (a Type of Immune Cell) Lymphoma That Has Returned After Treatment or Does Not Respond to Treatment
  • Official Title: A Phase 1b/2 Study of Hu5F9-G4 (Magrolimab) in Combination With Mogamulizumab in Relapsed/Refractory Treated T-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2020-06710
  • SECONDARY ID: NCI-2020-06710
  • SECONDARY ID: PHII-203
  • SECONDARY ID: 10384
  • SECONDARY ID: 10384
  • SECONDARY ID: UM1CA186717
  • NCT ID: NCT04541017

Conditions

  • Recurrent Mycosis Fungoides
  • Recurrent Mycosis Fungoides and Sezary Syndrome
  • Recurrent Sezary Syndrome
  • Refractory Mycosis Fungoides
  • Refractory Mycosis Fungoides and Sezary Syndrome
  • Refractory Sezary Syndrome
  • Sezary Syndrome
  • Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVA1 Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVA2 Mycosis Fungoides and Sezary Syndrome AJCC v8
  • Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v8

Interventions

DrugSynonymsArms
MagrolimabHu5F9-G4Arm I (magrolimab, mogamulizumab), Phase Ib and Phase II
MogamulizumabImmunoglobulin G1, Anti-(CC Chemokine Receptor CCR4) (Human-Mouse Monoclonal KW-0761 Heavy Chain), Disulfide With Human-Mouse Monoclonal KW-0761 Kappa-Chain, Dimer, KM8761, KW-0761, Mogamulizumab-kpkc, PoteligeoArm I (magrolimab, mogamulizumab), Phase Ib and Phase II

Purpose

This phase Ib/II trial identifies the best dose and possible benefits and/or side effects of magrolimab when given in combination with mogamulizumab in treating patients with stage IB-IV mycosis fungoides or Sezary syndrome types of T-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Magrolimab and mogamulizumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Treatment with magrolimab in combination with mogamulizumab may stabilize cancer for longer period than the usual treatment in patients with relapsed/refractory T-cell lymphoma who have been previously treated.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To characterize the safety and toxicity profile and to determine a safe recommended phase
      2 dose (RP2D) of Hu5F9-G4 (magrolimab) when given in combination with mogamulizumab. (Phase
      I) II. To compare the proportion of patients who achieve a partial or complete response
      lasting at least 6 months (ORR6) of the combination of Hu5F9-G4 (magrolimab) and
      mogamulizumab versus mogamulizumab alone. (Phase II)

      SECONDARY OBJECTIVES:

      I. To observe and record anti-tumor activity. (Phase I)

      II. To compare the efficacy of the combination of Hu5F9-G4 (magrolimab) and mogamulizumab
      versus mogamulizumab alone with respect to the following endpoints (Phase II):

      IIa. Overall response rate (ORR); overall response rate lasting at least 4 months (ORR4);
      overall response rate lasting at least 12 months (ORR12).

      IIb. Duration of response (DOR). IIc. Progression-free survival (PFS). IId. Time to next
      treatment (TTNT).

      EXPLORATORY OBJECTIVES:

      I. To identify potential biomarkers that correlate with response to mogamulizumab and
      Hu5F9-G4 (magrolimab) including (Phase I and II):

      Ia. Expression of CCR4. Ib. Somatic mutations and germline polymorphisms. Ic. Phenotyping of
      lymphoma and immune microenvironment. Id. Functional assay of phagocytosis.

      OUTLINE: This is a phase Ib, dose de-escalation study of magrolimab followed by a phase II
      study. Patients in the phase Ib study receive treatment as in Arm I. Patients in the phase II
      study are randomized to Arm I or Arm II.

      ARM I: Patients receive magrolimab intravenously (IV) over 2-3 hours weekly during cycles
      1-2, then every 2 weeks (Q2W) during cycles 3-12. Patients also receive mogamulizumab IV over
      at least 60 minutes weekly during cycle 1, then Q2W during cycles 2-12. Cycles repeat every
      28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive mogamulizumab IV over at least 60 minutes weekly during cycle 1,
      then Q2W during cycles 2-12. Cycles repeat every 28 days for up to 12 cycles in the absence
      of disease progression or unacceptable toxicity. Patients who have received at least 2 full
      treatment cycles and have progressive disease (PD) or have received at least 6 full treatment
      cycles and have stable disease (SD) may crossover to Arm I.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (magrolimab, mogamulizumab), Phase Ib and Phase IIExperimentalPatients receive magrolimab IV over 2-3 hours weekly during cycles 1-2, then Q2W during cycles 3-12. Patients also receive mogamulizumab IV over at least 60 minutes weekly during cycle 1, then Q2W during cycles 2-12. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
  • Magrolimab
  • Mogamulizumab
Arm II (mogamulizumab), Phase IIActive ComparatorPatients receive mogamulizumab IV over at least 60 minutes weekly during cycle 1, then Q2W during cycles 2-12. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients who have received at least 2 full treatment cycles and have PD or have received at least 6 full treatment cycles and have SD may crossover to Arm I.
  • Magrolimab

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of either MF or SS by the World Health Organization (WHO) 2016
             classification (Swerdlow et al., 2017), stage IB-IV by modified International Society
             for Cutaneous Lymphomas (ISCL)/ European Organization of Research and Treatment of
             Cancer (EORTC) classification (Olsen et al., 2011), without large cell transformation
             (LCT) at the time of screening. Patients with a history of prior LCT are permitted

          -  Patients must have had at least one prior course of systemic therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Hemoglobin >= 9.5 g/dL and transfusion independence (defined as not requiring more
             than 2 units of red blood cell [RBC] transfusions during the 4-week period prior to
             screening)

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 75,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for subjects
             with Gilbert's syndrome or genetic equivalent

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 x institutional ULN

          -  Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 by the Cockcroft-Gault formula

          -  Patients must meet the following minimum wash-out window from previous treatments to
             the first treatment

               -  >= 3 weeks for systemic anti-cancer therapies

               -  >= 2 weeks for phototherapy, local radiation therapy, topical high potency
                  corticosteroid, topical retinoid, topical nitrogen mustard, or topical toll-like
                  receptor (TLR)-agonist

               -  >= 12 weeks for total skin electron beam therapy Participants with rapidly
                  progressive malignant disease may be enrolled prior to completion of the above
                  periods with approval of the protocol director

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated

          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For patients with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load

          -  Patients with treated brain metastases are eligible if follow-up brain imaging after
             central nervous system (CNS)-directed therapy shows no evidence of progression for a
             minimum of 3 months

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  The effects of Hu5F9-G4 (magrolimab) on the developing human fetus are unknown. For
             this reason and because monoclonal antibody agents as well as other therapeutic agents
             used in this trial (mogamulizumab) are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry and for the duration of study
             participation and continue for 4 months after the last dose of both Hu5F9-G4
             (magrolimab) and mogamulizumab. Effective contraception is defined as oral
             contraceptives, double barrier method (condom plus spermicide or diaphragm plus
             spermicide) or practice true abstinence from heterosexual intercourse. Women of
             childbearing potential includes any female who has experienced menarche and has not
             undergone successful surgical sterilization or is not postmenopausal (defined as
             amenorrhea >= 12 consecutive months). Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol who are
             sexually active with women of childbearing potential and who have not had vasectomies
             must also agree to use adequate contraception prior to the study, for the duration of
             study participation, and 4 months after completion of Hu5F9-G4 (magrolimab)
             administration

          -  Female patients of childbearing potential must not be nursing or planning to be
             pregnant and must have a negative urine or serum pregnancy test within 30 days before
             randomization and within 72 hours before the first administration of study treatment

               -  Female patients of childbearing potential must be willing to use one highly
                  effective method of contraception during the study and continue for 4 months
                  after the last dose of study treatment

               -  Male patients who are sexually active with a woman of childbearing potential
                  (WOCBP) and who have not had vasectomies must be willing to use a barrier method
                  of contraception (condom plus spermicidal gel) and refrain from sperm donation
                  during the study and for 4 months after the last dose of study treatment. If the
                  partner is pregnant, male patients must use barrier method contraception (condom)
                  during the study and for 4 months after the last dose of study treatment to
                  prevent fetal exposure to study treatment

          -  Ability to understand and the willingness to sign a written informed consent document.
             Participants with impaired decision-making capacity (IDMC) who have a
             legally-authorized representative (LAR) and/or family member available will also be
             eligible

          -  Willing to comply with clinic visit schedule and procedures including mandatory
             biopsies

        Exclusion Criteria:

          -  Prior treatment with Hu5F9-G4 (magrolimab) or any agent targeting CD47-SIRPalpha

          -  Prior treatment with mogamulizumab

          -  Patients who have not recovered from adverse events due to prior anti-cancer therapy
             (i.e., have residual toxicities > grade 1) with the exception of alopecia and
             lymphopenia (any grade permitted). Residual peripheral neuropathy must have improved
             to grade 2 or better

          -  Patients who are receiving any other investigational agents

          -  Allogeneic hematopoietic stem cell transplant recipients with any graft-versus-host
             disease within the previous 3 months or requiring immunosuppression

          -  Active autoimmune disease that has required systemic immunosuppressive medication
             within the previous 3 months

          -  Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who have no
             active signs of active infection, and whose last active infection was more than 6
             months ago, may enter the study, and should continue to take the prescribed medication
             for the duration of the study

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Hu5F9-G4 (magrolimab), other monoclonal antibodies, or other agents
             (mogamulizumab) used in study

          -  Significant cardiopulmonary disease defined as

               -  Acute myocardial infarction within the last 6 months

               -  Unstable angina

               -  Congestive heart failure New York Heart Association (NYHA) class III-IV

          -  Patients with uncontrolled intercurrent illness requiring antibiotics. Patients on
             prophylactic antibiotics for non-complicated staphylococcus colonization/infection are
             eligible

          -  Patients with new or progressive brain metastases (active brain metastases) or
             leptomeningeal disease are excluded

          -  Patients with psychiatric illness/social situations or substance abuse that would
             limit compliance with study requirements

          -  Pregnant women are excluded from this study because Hu5F9-G4 (magrolimab) is
             monoclonal antibody agent with the potential for teratogenic or abortifacient effects.
             Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with Hu5F9-G4 (magrolimab), breastfeeding should
             be discontinued if the mother is treated with Hu5F9-G4 (magrolimab). These potential
             risks may also apply to other agents used in this study (mogamulizumab)

          -  Patients with RBC transfusion dependence, defined as requiring more than 2 units of
             RBCs transfused during the 4-week period prior to screening. RBC transfusions are
             permitted during the screening period and prior to enrollment

          -  Patients with prior autoimmune thrombocytopenia, hemolytic anemia or Evans syndrome
             requiring treatment in the last 12 months

          -  Patients on the following medications at the time of enrollment:

               -  Immunotherapy or immunosuppressive drugs (e.g. chemotherapy or systemic
                  corticosteroids) EXCEPT for the following:

                    -  Intranasal, inhaled, or local steroid injection (e.g. intra-articular
                       injection)

                    -  Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or
                       equivalent, if patient has been on a stable dose for at least 2 weeks prior
                       to the first treatment

                    -  Low and medium potency topical corticosteroids are permitted if patient has
                       been on a stable dose for at least 2 weeks prior to the first treatment

                    -  Steroids as premedication for hypersensitivity reactions (e.g. computed
                       tomography [CT] scan premedication)

               -  Growth factors (granulocyte colony stimulating factor or granulocyte macrophage
                  colony stimulating factor) EXCEPT for erythropoietin and darbepoetin alpha

               -  Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or
                  known to potentially interfere with major organ function (e.g. hypericin)

          -  Live vaccines are not allowed while participating in the trial. Examples of live
             vaccines include, but are not limited to, the following: measles, mumps, rubella,
             chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), typhoid (oral)
             vaccine, and intranasal influenza vaccines (e.g., Flu-Mist). However, seasonal
             influenza vaccines for injection are generally killed virus vaccines and are allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase 2 dose (RP2D) of magrolimab when given in combination with mogamulizumab (Phase Ib)
Time Frame:Up to 4 weeks from the first infusion of magrolimab (priming infusion)
Safety Issue:
Description:Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response >= 6 months. Will use a stratified Cochran-Mantel-Haenszel chi-squared test to compare between-group differences in ORR6 proportion. Will also conduct a secondary analysis on the intent-to-treat population (all patients randomized to a therapy and assigned a study number) and an efficacy evaluable set (all patients who received the first 12 weeks of treatment and completed the week 12 response assessment).

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Defined as the proportion of patients who have a partial or complete response to therapy as defined by the global response score. Will be assessed by the chi-squared method.
Measure:Overall response rate at 4 months (ORR4)
Time Frame:At 4 months
Safety Issue:
Description:Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response >= 4 months. Will be assessed by the chi-squared method.
Measure:Overall response rate at 12 months (ORR12)
Time Frame:At 12 months
Safety Issue:
Description:Will be defined as the proportion of patients who have a partial or complete response to therapy AND a duration of response >= 12 months. Will be assessed by the chi-squared method.
Measure:Progression-free survival (PFS)
Time Frame:From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Safety Issue:
Description:Will be assessed by the Kaplan-Meier method and the log-rank test.
Measure:Duration of response (DOR)
Time Frame:From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrence or progressive disease is objectively documented, assessed up to 2 years
Safety Issue:
Description:Will be assessed by the Kaplan-Meier method and the log-rank test.
Measure:Time to next treatment (TTNT)
Time Frame:From the start of treatment on this protocol to time of the next anti-neoplastic therapy, assessed up to 2 years
Safety Issue:
Description:Will be assessed by the Kaplan-Meier method and the log-rank test.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

May 4, 2021