Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

Multiple Myeloma Clinical Trial

Official title:

Phase II Study of Shortened-duration Tacrolimus Following Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Malignancies That Are Challenging to Engraft

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02556931
• Other study ID #: J15165
• Secondary ID: IRB00080399P01CA
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: April 2021

Study information

• Verified date: November 2022
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To see if it is possible to use short-duration tacrolimus after a peripheral blood stem cell transplant in certain malignancies that are considered difficult to engraft.

Description:

The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug (an immunosuppressant) given after transplant to help prevent certain complications, can be given safely for a shorter period of time than it has been in the past. The experiences with immunosuppression duration with other allogeneic HSCT platforms cannot be directly extrapolated to the high-dose posttransplantation cyclophosphamide platform (another type of immunosuppressant given after transplant to help prevent GVHD). There are presently no published data on the minimum required duration of tacrolimus after nonmyeloablative HSCT that includes high-dose Cy as part of postgrafting immunosuppression. The effectiveness of high-dose posttransplantation Cy in GVHD prevention, however, permits the investigation of this question. At the present time there are few or no cures for diseases studied on this trial outside of a bone marrow or peripheral blood transplant. The peripheral blood for this transplant comes from a relative who is a half-match or "haplo" match to the participant. Possible donors include parents, siblings, and children. In order to help the bone marrow grow, or "take", inside the body, participants will receive chemotherapy and radiation before the transplant. After the transplant participants will receive high doses of cyclophosphamide (Cytoxan®) along with other medications to lower the immune system, such as tacrolimus. These medications may lower the risk of graft versus host disease (GVHD) and of rejection of the peripheral blood graft.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: April 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a 10/10 matched unrelated donor

• Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature; small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion or with progression < 6 months after a second or greater treatment regimen; T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial response or better; Hematologic malignancy in complete remission with minimal residual disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing

• Any previous autologous transplant must have occurred > 3 months ago

• Left ventricular ejection fraction (LVEF) >= 35%, or shortening fraction > 25%

• Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis)

• AST and ALT <= 5 x institutional upper limit of normal

• FEV1 and FVC >= 40% of predicted; if unable to perform pulmonary function testing, oxygen saturation > 92% on room air

• ECOG performance status <= 2, or Karnofsky/Lansky status >= 60

Exclusion Criteria:

• Pregnancy or active breastfeeding

• Uncontrolled active infection

• Previous allogeneic transplant

• Active extramedullary leukemia or active central nervous system (CNS) malignant disease

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Chronic Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Chronic Myeloproliferative Disorders
• Essential Thrombocythemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Leukemia, Plasma Cell
• Leukemia, Prolymphocytic
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myelofibrosis
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Paraproteinemias
• Plasma Cell Dyscrasia
• Plasma Cell Leukemia
• Plasma Cell Neoplasm
• Plasmacytoma
• Polycythemia
• Polycythemia Vera
• Prolymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Fludarabine
Days -6 through -2: 30 mg/m^2 IV daily
• Cyclophosphamide
Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

Radiation:
• Total body irradiation
Day -1: 200 cGy in a single fraction

Drug:
• Tacrolimus
Start on Day 5 through either Day 60 or Day 90 depending on cohort assignment. May be continued through Day 180 depending on GVHD status.
• Mycophenolate mofetil
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort)	This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.	Day 90
Primary	Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D60 Cohort)	This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.	Day 60
Secondary	Number of Participants With Grades III-IV Acute GVHD, Days 90-180 (D90)	Number of participants who experience grade III or IV acute GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.	Between Day 90 and Day 180
Secondary	Number of Participants With Grades III-IV Acute GVHD, Days 60-180 (D60)	Number of participants who experience grade III or IV acute GVHD between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.	Between Day 60 and Day 180
Secondary	Number of Participants With Chronic GVHD, Days 90-180 (D90)	Number of participants who experience chronic GVHD requiring additional immunosuppressive therapy between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.	Between Day 90 and Day 180
Secondary	Number of Participants With Chronic GVHD, Days 60-180 (D60)	Number of participants who experience chronic GVHD requiring additional immunosuppressive therapy between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.	Between Day 60 and Day 180
Secondary	Number of Participants Who Experience Graft Failure, Days 90-180 (D90)	Number of participants who experience graft failure between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.	Between Day 90 and Day 180
Secondary	Number of Participants Who Experience Graft Failure, Days 60-180 (D60)	Number of participants who experience graft failure between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.	Between Day 60 and Day 180
Secondary	Number of Participants Who Experience Disease Relapse, Days 90-180 (D90)	Number of participants who experience disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.	Between Day 90 and Day 180
Secondary	Number of Participants Who Experience Disease Relapse, Days 60-180 (D60)	Number of participants who experience disease relapse between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.	Between Day 60 and Day 180
Secondary	Number of Participants Who Experience Non-relapse Mortality, Days 90-180 (D90)	Number of participants who die for any reason other than disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.	Between Day 90 and Day 180
Secondary	Number of Participants Who Experience Non-relapse Mortality, Days 60-180 (D60)	Number of participants who die for any reason other than disease relapse between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.	Between Day 60 and Day 180
Secondary	Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D90)	Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D60)	Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Number of Participants With Severe Chronic GVHD, Day 360 (D90)	Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Number of Participants With Severe Chronic GVHD, Day 360 (D60)	Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Number of Participants Who Experience Graft Failure, Day 360 (D90)	Number of participants who experience graft failure by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Number of Participants Who Experience Graft Failure, Day 360 (D60)	Number of participants who experience graft failure by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Participants Who Experience Relapse, Day 360 (D90)	Number of participants who experience disease relapse by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Participants Who Experience Relapse, Day 360 (D60)	Number of participants who experience disease relapse by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Participants Who Experience Non-relapse Mortality, Day 360 (D90)	Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.	Day 360
Secondary	Number of Participants Who Experience Non-relapse Mortality, Day 360 (D60)	Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.	Day 360