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Study of Ipilimumab After Stem Cell Transplantation in People With Relapsed/Refractory Multiple Myeloma

Phase 1
Terminated
Conditions
Relapsed/Refractory Multiple Myeloma
Interventions
Registration Number
NCT04635735
Lead Sponsor
Memorial Sloan Kettering Cancer Center
Brief Summary

This study will test the safety of ipilimumab to see what effects, if any, the drug has when used as maintenance therapy for people with relapsed/refractory multiple myeloma who have received chemotherapy and allogeneic hematopoietic stem cell transplant (AHCT). The investigators also want to find out whether giving ipilimumab after chemotherapy and AHCT is a better way to control the multiple myeloma than chemotherapy and AHCT alone.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
Inclusion Criteria

Inclusion Criteria prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT):

  • Willing and able to participate as a research subject and provide informed consent (Note: an LAR may sign the consent form on the partipant's behalf)

  • Diagnosis of relapsed refractory multiple myeloma defined as more than 2 lines of prior therapy with at least a very good partial remission to most recent salvage therapy.

    • Patients should have R-ISS stage II or III disease at diagnosis or high risk cytogenetics by IMWG criteria (t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q)) at any time since diagnosis

Note:. A line of therapy is treatment between diagnosis and progression or between two progressions

  • Eligible for CD34-selected HSCT according to MSKCC adult BMT guidelines.

  • Have a 10/10 matched donor

  • Age ≥ 21, < 73 years.

  • Karnofsky (adult) Performance Status ≥ 70%.

  • Patients must have adequate organ function measured by:

    1. Cardiac: LVEF at rest must be ≥ 50%

    2. Hepatic:

      • < 3x ULN ALT
      • < 1.5 ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
    3. Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min

    4. Pulmonary: DLCO > 50% of predicted (corrected for hemoglobin).

Inclusion Criteria prior to Ipilimumab:

  • Non progressive myeloma (partial response or better) as defined by International Myeloma Working Group (IMWG) criteria

  • Engraftment of all cell lines without transfusion dependence, defined as:

    • absolute neutrophil count > 1.0K/mcL x 3 consecutive days
    • platelets > 50K/mcLx 7 consecutive days without platelet transfusion
    • no platelet or RBC transfusions within the preceding 7 days
  • ≥ 80% donor chimerism in the bone marrow

Exclusion Criteria

Exclusion Criteria prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT):

  • Patients ineligible for therapy with ipilimumab, for example:.

    1. Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive medications at enrollment. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    2. History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).
  • Female patients who are pregnant or breast-feeding.

  • Patients with plasma cell leukemia at the time of diagnosis.

  • Patients who have undergone prior allogeneic hematopoietic stem cell transplantation.

  • Patients who have had a previous malignancy that is not in remission.

Exclusion Criteria prior to Ipilimumab:

  • Active infection or treatment for infection (patients on Cytomegalovirus (CMV) therapy will be considered eligible; patients with CMV viremia by PCR or disease with end-organ involvement will not be eligible)

  • Active GVHD of any grade or prior grade 3-4 GVHD

  • Active immune suppression, defined as:

    • active use of calcineurin inhibitors, mycophenolate mofetil, or other immunomodulators
    • steroid dosing exceeding 10 mg/d prednisone or equivalent
  • Receiving immunomodulatory agents (ex. thalidomide, lenalidomide, pomalidomide)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ipilimumab After Stem Cell TransplantationIpilimumabThe patient will be admitted to a single room on the Adult Transplantation Service and allogeneic CD34-selected PBSC or marrow transplantation performed as per MSKCC adult BMT guidelines. Patients will be evaluated at approximately day 100 (±2 weeks) after allo-HSCT.
Primary Outcome Measures
NameTimeMethod
Phase I: Maximum Tolerated Dose of Ipilimumab1 year

A maximum of 12 patients will be accrued and DLTs will be assessed in these patients. If any DLT is observed in more than one of the six patient cohort, a lower dose of ipilimumab will be evaluated in a new six patient cohort.

Phase II: Progression Free Survival (PFS)2 years

criteria of the International Myeloma Working Group

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

🇺🇸

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering Commack (Limited Protocol Activities)

🇺🇸

Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

🇺🇸

Harrison, New York, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

🇺🇸

Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

🇺🇸

Uniondale, New York, United States

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