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

NCT02556931 | Completed Phase 2 Results

• 3 other identifiers: J15165IRB00080399P01CA015396
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (20)

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

  Between Day 90 and Day 180

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

  Between Day 60 and Day 180

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

  Between Day 90 and Day 180

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

  Between Day 60 and Day 180

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

  Between Day 90 and Day 180

Study Arms (2)

PBSCT D90

EXPERIMENTAL

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.

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

PBSCT D60

EXPERIMENTAL

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 60 or Day 180 depending on GVHD status.

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

Interventions

Fludarabine DRUG

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

Also known as: Fludara

PBSCT D60; PBSCT D90

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Cy, CTX

PBSCT D60; PBSCT D90

Total body irradiation RADIATION

Day -1: 200 cGy in a single fraction

Also known as: TBI

PBSCT D60; PBSCT D90

Tacrolimus DRUG

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.

Also known as: Prograf, FK506, FK-506

PBSCT D60; PBSCT D90

Mycophenolate mofetil DRUG

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

Also known as: MMF, CellCept

PBSCT D60; PBSCT D90

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnancy or active breastfeeding
• Uncontrolled active infection
• Previous allogeneic transplant
• Active extramedullary leukemia or active central nervous system (CNS) malignant disease

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias; Primary Myelofibrosis; Polycythemia Vera; Thrombocythemia, Essential; Leukemia, Plasma Cell

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Amy Dezern
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

adezern1@jhmi.edu

410-502-7208

Study Officials

• Amy E DeZern, MD

  410-502-7208

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 22, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: November 3, 2022
• Results First Posted: November 3, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)