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

Primary Purpose

Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Small Lymphocytic Lymphoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fludarabine

Cyclophosphamide

Total body irradiation

Tacrolimus

Mycophenolate mofetil

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring immunosuppression, nonmyeloablative, non-myeloablative, allogeneic, tacrolimus, peripheral blood, cyclophosphamide, mycophenolate mofetil

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

PBSCT D90

PBSCT D60

Arm Description

Non-myeloablative peripheral blood stem cell transplant (PBSCT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Tacrolimus will be stopped at either Day 90 or Day 180 depending on GVHD status.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort)

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D60 Cohort)

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Number of Participants Who Experience Relapse, Day 360 (D90)

Number of participants who experience disease relapse by Day 360. All participants are evaluable.

Number of Participants Who Experience Relapse, Day 360 (D60)

Number of participants who experience disease relapse by Day 360. All participants are evaluable.

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.

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.

Full Information

NCT ID

NCT02556931

First Posted

September 21, 2015

Last Updated

November 2, 2022

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02556931

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

December 2015 (Actual)

Primary Completion Date

April 2021 (Actual)

Study Completion Date

April 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Small Lymphocytic Lymphoma, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Chronic Myeloid Leukemia, Chronic Myeloproliferative Disorders, Multiple Myeloma, Plasma Cell Neoplasm, Plasma Cell Dyscrasia, Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, Plasma Cell Leukemia

Keywords

immunosuppression, nonmyeloablative, non-myeloablative, allogeneic, tacrolimus, peripheral blood, cyclophosphamide, mycophenolate mofetil

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

117 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PBSCT D90

Arm Type

Experimental

Arm Description

Arm Title

PBSCT D60

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludara

Intervention Description

Days -6 through -2: 30 mg/m^2 IV daily

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan, Cy, CTX

Intervention Description

Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

Intervention Type

Radiation

Intervention Name(s)

Total body irradiation

Other Intervention Name(s)

TBI

Intervention Description

Day -1: 200 cGy in a single fraction

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

Prograf, FK506, FK-506

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

MMF, CellCept

Intervention Description

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Primary Outcome Measure Information:

Title

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort)

Description

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.

Time Frame

Day 90

Title

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D60 Cohort)

Description

This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.

Time Frame

Day 60

Secondary Outcome Measure Information:

Title

Number of Participants With Grades III-IV Acute GVHD, Days 90-180 (D90)

Description

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.

Time Frame

Between Day 90 and Day 180

Title

Number of Participants With Grades III-IV Acute GVHD, Days 60-180 (D60)

Description

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.

Time Frame

Between Day 60 and Day 180

Title

Number of Participants With Chronic GVHD, Days 90-180 (D90)

Description

Time Frame

Between Day 90 and Day 180

Title

Number of Participants With Chronic GVHD, Days 60-180 (D60)

Description

Time Frame

Between Day 60 and Day 180

Title

Number of Participants Who Experience Graft Failure, Days 90-180 (D90)

Description

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.

Time Frame

Between Day 90 and Day 180

Title

Number of Participants Who Experience Graft Failure, Days 60-180 (D60)

Description

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.

Time Frame

Between Day 60 and Day 180

Title

Number of Participants Who Experience Disease Relapse, Days 90-180 (D90)

Description

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.

Time Frame

Between Day 90 and Day 180

Title

Number of Participants Who Experience Disease Relapse, Days 60-180 (D60)

Description

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.

Time Frame

Between Day 60 and Day 180

Title

Number of Participants Who Experience Non-relapse Mortality, Days 90-180 (D90)

Description

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.

Time Frame

Between Day 90 and Day 180

Title

Number of Participants Who Experience Non-relapse Mortality, Days 60-180 (D60)

Description

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.

Time Frame

Between Day 60 and Day 180

Title

Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D90)

Description

Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D60)

Description

Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Number of Participants With Severe Chronic GVHD, Day 360 (D90)

Description

Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Number of Participants With Severe Chronic GVHD, Day 360 (D60)

Description

Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Number of Participants Who Experience Graft Failure, Day 360 (D90)

Description

Number of participants who experience graft failure by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Number of Participants Who Experience Graft Failure, Day 360 (D60)

Description

Number of participants who experience graft failure by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Participants Who Experience Relapse, Day 360 (D90)

Description

Number of participants who experience disease relapse by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Participants Who Experience Relapse, Day 360 (D60)

Description

Number of participants who experience disease relapse by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Participants Who Experience Non-relapse Mortality, Day 360 (D90)

Description

Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.

Time Frame

Day 360

Title

Number of Participants Who Experience Non-relapse Mortality, Day 360 (D60)

Description

Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.

Time Frame

Day 360

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amy E DeZern, MD

Organizational Affiliation

410-502-7208

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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