Allo HSCT Using RIC for Hematological Diseases

University of Minnesota (UMN)

Status and phase

Completed

Phase 2

Conditions

Myeloproliferative Syndromes

Acute Myelogenous Leukemia

B-Cell Lymphoma

Small Lymphocytic Lymphoma

Chronic Myelogenous Leukemia

Lymphoplasmacytic Lymphoma

Mantle-Cell Lymphoma

Myelodysplastic Syndromes

Burkitt's Lymphoma

Plasma Cell Leukemia

Acute Lymphocytic Leukemia

Multiple Myeloma

Non-Hodgkin's Lymphoma

Lymphoblastic Lymphoma

Follicular Lymphoma

Hematological Diseases

Chronic Lymphocytic Leukemia

Prolymphocytic Leukemia

Treatments

Drug: MMF

Drug: Cyclophosphamide

Drug: ATG

Drug: Fludarabine

Biological: Related or Unrelated Bone Marrow Cells

Drug: Allopurinol

Radiation: TBI

Biological: Peripheral Blood Stem Cells

Drug: Tacrolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT02661035

2015LS152

Details and patient eligibility

About

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. The primary objective is to evaluate rates of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD with an updated GVHD prophylaxis of tacrolimus and mycophenolate mofetil (MMF) with a non-myeloablative preparative regimen in persons with hematologic malignancies.

Enrollment

156 patients

Sex

All

Ages

Under 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age, Performance Status, and Graft Criteria
- Age 0 to 70 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
- Patients ≥ 70 and ≤ 75 years of age may be eligible if they have a HCT-CI Co-Morbidity score ≤ 2
- Must be ≥ 3 months after prior myeloablative transplant, if applicable
- 5/6 or 6/6 related donor match or a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor marrow and/or PBSC donor match per current institutional guidelines Related donors will be evaluated and collected per MT2012-14C; Unrelated donors will be identified and collected per usual procedures
Eligible Diseases
- Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
- Acute Lymphocytic Leukemia (ALL): factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
- Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
- Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
- Myelodysplasia (MDS) requiring transplant as defined as: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology.
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, NK cell malignancies are eligible after initial therapy in CR1+ or PR1+.
- Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
- Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
- Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
- Myeloproliferative Syndromes
Organ Function Criteria Adequate organ function is defined as:
- Liver: AST and ALT < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
- Renal: Creatinine ≤ 2.0 mg/dl (adults) and estimated glomerular filtration rate (GFR) ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated glomerular filtration rate (GFR) > 40 mL/min.
- Albumin > 2.5 g/dL
- Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%.
- Pulmonary: DLCOcorr ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with or without exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
Females of child bearing potential and sexually active males must agree to use adequate birth control during study treatment
Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

Exclusion criteria

Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Untreated active infection
Active CNS disease
Active HIV infection or known HIV positive serology
Congenital bone marrow failure syndrome
Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of TBI
CML in refractory blast crisis
Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
Multiple myeloma progressive on salvage chemotherapy

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

156 participants in 1 patient group

Reduced Intensity Conditioning

Experimental group

Description:

Non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion

Treatment: